Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2021
Pulmonary hypertension is a rare disease with high morbidity and mortality which mainly affects w... more Pulmonary hypertension is a rare disease with high morbidity and mortality which mainly affects women of reproductive age. Despite recent advances in understanding the pathogenesis of pulmonary hypertension, the high heterogeneity in the presentation of the disease among different patients makes it difficult to make an accurate diagnosis and to apply this knowledge to effective treatments. Therefore, new studies are required to focus on translational and personalized medicine to overcome the lack of specificity and efficacy of current management. Here, we review the majority of public databases storing 'omics' data of pulmonary hypertension studies, from animal models to human patients. Moreover, we review some of the new molecular mechanisms involved in the pathogenesis of pulmonary hypertension, including non-coding RNAs and the application of 'omics' data to understand this pathology, hoping that these new approaches will provide insights to guide the way to personalized diagnosis and treatment.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Healthy mitochondrial function is imperative for most tissues, but especially those with a high e... more Healthy mitochondrial function is imperative for most tissues, but especially those with a high energy demand. Robust evidence linking mitochondrial dysfunction with cardiovascular disease has demonstrated that mitochondrial activity is highly relevant to cardiac muscle performance. Mitochondrial homeostasis is maintained through coordination among the processes that comprise the so-called mitochondrial dynamics machinery. The most-studied elements of cardiac mitochondrial dynamics are mitochondrial fission and fusion, biogenesis and degradation. Selective autophagic removal of mitochondria (mitophagy) is essential for clearing away defective mitochondria but can lead to cell damage and death if not tightly controlled. In cardiovascular cells such as cardiomyocytes and cardiac fibroblasts, mitophagy is involved in metabolic activity, cell differentiation, apoptosis and other physiological processes related to major phenotypic changes. Modulation of mitophagy has detrimental and/or beneficial outcomes in various cardiovascular diseases, suggesting that a deeper understanding of the mechanisms underlying mitochondrial degradation in the heart could provide valuable clinical insights. Here, we discuss current evidence supporting the role of mitophagy in cardiac pathophysiology, with an emphasis on different research models and their interpretations; basic concepts related to this selective autophagy; and the most commonly used experimental approaches for studying this mechanism. Finally, we provide a comprehensive literature analysis on the role of mitophagy in heart failure, ischemia/reperfusion, diabetic cardiomyopathy and other cardiovascular diseases, as well as its potential biomedical applications.
En el modelo preclínico de insuficiencia cardíaca por disfunción sistólica en ratón (coartación d... more En el modelo preclínico de insuficiencia cardíaca por disfunción sistólica en ratón (coartación de aorta torácica) la velocidad de flujo carotídeo determinada precozmente se asocia a función ventricular izquierda tardía
A 51-year-old Hispanic female with no relevant medical history exhibited progressive dyspnoea on ... more A 51-year-old Hispanic female with no relevant medical history exhibited progressive dyspnoea on exertion without haemoptysis, fever, malaise, skin lesions, or arthritis. She denied having oral or genital aphthae, as well as ocular or neurological diseases. Physical examination showed jugular ingurgitation, a wide splitting of the second heart sound, with a loud pulmonary component. Lung auscultation was normal. She had no clubbing or peripheral oedema. Transthoracic echocardiogram revealed severe pulmonary hypertension (PH), with an estimated systolic pulmonary artery pressure of 91 mmHg, and signs of chronic right ventricle pressure overload. Computed tomography angiography revealed pulmonary arteries with severe tortuosity and multiple foci of dilatation and stenosis, showing a ‘string of beads’ appearance, without evidence of pulmonary embolism (Figure 1). There were no lesions either in the carotid or renal arteries, suggestive of fibromuscular dysplasia. Complete blood count, C reactive protein, and sedimentation rate were normal. A serological evaluation for systemic vasculitis and connective tissue diseases was negative.
It is unknown why heart failure progresses even when patients are treated with the best therapy a... more It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.
Hypertension (HTN) is a public health concern and a major preventable cause of cardiovascular dis... more Hypertension (HTN) is a public health concern and a major preventable cause of cardiovascular disease (CVD). When uncontrolled, HTN may lead to adverse cardiac remodeling, left ventricular hypertrophy, and ultimately, heart failure. Regular aerobic exercise training exhibits blood pressure protective effects, improves myocardial function, and may reverse pathologic cardiac hypertrophy. These beneficial effects depend at least partially on improved mitochondrial function, decreased oxidative stress, endothelial dysfunction, and apoptotic cell death, which supports the general recommendation of moderate exercise in CVD patients. However, most of these mechanisms have been described on healthy individuals; the effect of moderate exercise on HTN subjects at a cellular level remain largely unknown. We hypothesized that hypertension in adult spontaneously hypertensive rats (SHRs) reduces the mitochondrial response to moderate exercise in the myocardium. Methods: Eight-month-old SHRs and their normotensive control—Wistar-Kyoto rats (WKYR)—were randomly assigned to moderate exercise on a treadmill five times per week with a running speed set at 10 m/min and 15° inclination. The duration of each session was 45 min with a relative intensity of 70–85% of the maximum O2 consumption for a total of 8 weeks. A control group of untrained animals was maintained in their cages with short sessions of 10 min at 10 m/min two times per week to maintain them accustomed to the treadmill. After completing the exercise protocol, we assessed maximum exercise capacity and echocardiographic parameters. Animals were euthanized, and heart and muscle tissue were harvested for protein determinations and gene expression analysis. Measurements were compared using a nonparametric ANOVA (Kruskal-Wallis), with post-hoc Dunn's test. Results: At baseline, SHR presented myocardial remodeling evidenced by left ventricular hypertrophy (interventricular septum 2.08 ± 0.07 vs. 1.62 ± 0.08 mm, p < 0.001), enlarged left atria (0.62 ± 0.1 mm vs. 0.52 ± 0.1, p = 0.04), and impaired diastolic function (E/A ratio 2.43 ± 0.1 vs. 1.56 ± 0.2) when compared to WKYR. Moderate exercise did not induce changes in ventricular remodeling but improved diastolic filling pattern (E/A ratio 2.43 ± 0.1 in untrained SHR vs. 1.89 ± 0.16 trained SHR, p < 0.01). Histological analysis revealed increased myocyte transversal section area, increased Myh7 (myosin heavy chain 7) expression, and collagen fiber accumulation in SHR-control hearts. While the exercise protocol did not modify cardiac size, there was a significant reduction of cardiomyocyte size in the SHR-exercise group. Conversely, titin expression increased only WYK-exercise animals but remained unchanged in the SHR-exercise group. Mitochondrial response to exercise also diverged between SHR and WYKR: while moderate exercise showed an apparent increase in mRNA levels of Ppargc1α, Opa1, Mfn2, Mff, and Drp1 in WYKR, mitochondrial dynamics proteins remained unchanged in response to exercise in SHR. This finding was further confirmed by decreased levels of MFN2 and OPA1 in SHR at baseline and increased OPA1 processing in response to exercise in heart. In summary, aerobic exercise improves diastolic parameters in SHR but fails to activate the cardiomyocyte mitochondrial adaptive response observed in healthy individuals. This finding may explain the discrepancies on the effect of exercise in clinical settings and evidence of the need to further refine our understanding of the molecular response to physical activity in HTN subjects.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018
Bone integrity depends on a finely tuned balance between bone synthesis by osteoblasts and resorp... more Bone integrity depends on a finely tuned balance between bone synthesis by osteoblasts and resorption by osteoclasts. The secretion capacity of mature osteoblasts requires strict control of proteostasis. Endoplasmic reticulum-associated degradation (ERAD) prevents the accumulation of unfolded ER proteins via dislocation to the cytosol and degradation by the proteasome. The ER membrane protein, homocysteine-inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (HERPUD1), is a key component of the ERAD multiprotein complex which helps to stabilize the complex and facilitate the efficient degradation of unfolded proteins. HERPUD1 expression is strongly up-regulated by the unfolded protein response and cellular stress. The aim of the current study was to establish whether HERPUD1 and ERAD play roles in osteoblast differentiation and maturation. We evaluated preosteoblastic MC3T3-E1 cell and primary rat osteoblast differentiation by measuring calcium deposit levels, alkali...
We report the first optical biosensor for the novel and important cardiac biomarker, galectin-3 (... more We report the first optical biosensor for the novel and important cardiac biomarker, galectin-3 (Gal3), using the anti-Gal3 antibody as a biorecognition element and surface plasmon resonance (SPR) for transducing the bioaffinity event. The immunosensing platform was built at a thiolated Au surface modified by self-assembling four bilayers of poly(diallyldimethylammonium chloride) and graphene oxide (GO), followed by the covalent attachment of 3-aminephenylboronic acid (3ABA). The importance of GO, both as the anchoring point of the antibody and as a field enhancer for improving the biosensor sensitivity, was critically discussed. The advantages of using 3ABA to orientate the anti-Gal3 antibody through the selective link to the Fc region were also demonstrated. The new platform represents an interesting alternative for the label-free biosensing of Gal3 in the whole range of clinically relevant concentrations (linear range between 10.0 and 50.0 ng mL, detection limit of 2.0 ng mL) wit...
Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, ear... more Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, early detection of atherosclerosis, the common pathophysiological mechanism underlying cardiovascular diseases remains elusive, and overt coronary artery disease or myocardial infarction is often the first clinical manifestation. Nanoparticles represent a novel strategy for prevention, diagnosis, and treatment of atherosclerosis, and new multifunctional nanoparticles with combined diagnostic and therapeutic capacities hold the promise for theranostic approaches to this disease. This review focuses on the development of nanosystems for therapy and diagnosis of subclinical atherosclerosis, coronary artery disease, and myocardial infarction and the evolution of nanosystems as theranostic tools. We also discuss the use of nanoparticles in noninvasive imaging, targeted drug delivery, photothermal therapies together with the challenges faced by nanosystems during clinical translation.
Galectin-3 levels in patients hospitalized for decompensated heart failure Background: Galectin-3... more Galectin-3 levels in patients hospitalized for decompensated heart failure Background: Galectin-3 (Gal-3) is a mediator of myocardial fibrosis involved in cardiac remodeling and a potential new prognosis marker in heart failure (HF). Aim: To measure Gal-3 at the moment of discharge in patients hospitalized for HF and its association with different variables. Material and Methods: Patients hospitalized for decompensated HF from four hospitals between August 2014 and March 2015, were included. Demographic, clinical and laboratory variables were recorded at the time of admission. At discharge, a blood sample was withdrawn to measure Gal-3 and brain natriuretic propeptide (Pro-BNP). Patients were separated in two groups, according to the level of Gal-3 (using a cutoff value of 17.8 ng/mL), comparing clinical and laboratory values between groups. Results: We included 52 patients with HF aged 70 ± 17 years (42% females).
Increased inflammation biomarkers plasma levels, including C-reactive protein (CRP), have been as... more Increased inflammation biomarkers plasma levels, including C-reactive protein (CRP), have been associated with the initiation and perpetuation of atrial fibrillation (AF). However, it is not known whether an increased CRP plasma level, without concomitant inflammation, is sufficient to induce AF. We investigated whether higher CRP plasma levels, determined by the presence of +219G>A CRP gene polymorphism, is associated with an increased risk of post-operative AF. One hundred and fifteen adult patients submitted to elective coronary surgery were genotyped for the CRP +219G>A polymorphism. CRP plasma levels were determined by enzyme-linked immunosorbent assay. CRP plasma levels before surgery were higher in GG than in GA+AA patients (3.4±3.1 vs. 1.7±1.8, p<0.015). Thirteen percent of the patients presented post-operative AF. Despite the positive correlation between the polymorphism and CRP levels, there was no significant difference in the occurrence of post-operative AF betw...
luis sepúlVeDa 7 en representación del grupo iCaro Frailty in patients admitted to hospital with ... more luis sepúlVeDa 7 en representación del grupo iCaro Frailty in patients admitted to hospital with acute decompensated heart failure Background: Frailty is a geriatric syndrome characterized by a progressive impairment in the subjects' ability to respond to environmental stress. Frailty is more commonly found in heart failure (HF) patients than in general population and it is an independent predictor of rehospitalization, emergency room visits and death. Aim: To estimate the prevalence of frailty in patients with decompensated HF admitted to four hospitals in Santiago, Chile. Material and Methods: Cross-sectional study. Subjects aged 60 or older consecutively admitted for decompensated HF to the study centers between August 2014 and March 2015 were included. Frailty was defined as the presence of three or more of the following criteria: unintended weight loss, muscular weakness, depression symptoms (exhaustion), reduced gait speed and low physical activity. Independent variables were tested for association using simple logistic regression. Variables associated with frailty (p < 0.05) were included in a multiple logistic regression model. Results: Seventy-nine subjects were included. The prevalence of frailty was 50.6%. Frail patients were mostly female (52.6%) and older than non-frail subjects (73.
Right atrium function and ventricular function have significant prognostic value in pulmonary art... more Right atrium function and ventricular function have significant prognostic value in pulmonary arterial hypertension patients. Acute changes in right ventricular synchrony and right atrium function postiloprost inhalation have not been evaluated. Cross-sectional study. Consecutive pulmonary arterial hypertension patients (group I from Nice classification) were included. Echocardiographic right atrium and right ventricular function pre- and postiloprost inhalation, including a right ventricular dyssynchrony index and right atrium function using speckle tracking, were performed in all patients. Twenty pulmonary arterial hypertension patients, 44±7 years and 90% females, were included. After iloprost inhalation, we observed a significant increment in right ventricular fractional area change and a significant decrease in right ventricular dyssynchrony index (21.4±5.6% vs 26.1±4.0 %, P=.007 and 79±44 vs 32±22 mseconds, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.01, respectively), also an improvement in right atrium reservoir function (8.6±3.1% vs 11.7±3.5 %, P=.002). Iloprost inhalation induces acute changes in right ventricular function, dyssynchrony, and right atrium performance that may add relevant clinical information in the management and risk stratification of pulmonary arterial hypertension patients.
Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary ... more Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary vasodilator therapies Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Long-term survival remains poor despite of advances in specific vasodilator therapy. Aim: To describe the survival rate in a cohort of PAH patients in two referral centers in Chile. Patients and Methods: One hundred fifteen patients aged 43 ± 15.6 years (85% females) with PAH qualified for this study. Their median pulmonary artery pressure was 55.4 ± 14 mmHg and their six minutes walking capacity was 368 ± 119 m. They were followed for 58 ± 0.4 months and their actual survival rates were compared with the estimated survival using the equation proposed by the French registry of PAH. Results: One, two and three year survival rates were 97, 94 and 89%, respectively. The observed survival rates were greater than the estimated survival. Conclusions: The improvement in survival rates observed in this cohort of patients is similar to what has been described in literature.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2021
Pulmonary hypertension is a rare disease with high morbidity and mortality which mainly affects w... more Pulmonary hypertension is a rare disease with high morbidity and mortality which mainly affects women of reproductive age. Despite recent advances in understanding the pathogenesis of pulmonary hypertension, the high heterogeneity in the presentation of the disease among different patients makes it difficult to make an accurate diagnosis and to apply this knowledge to effective treatments. Therefore, new studies are required to focus on translational and personalized medicine to overcome the lack of specificity and efficacy of current management. Here, we review the majority of public databases storing 'omics' data of pulmonary hypertension studies, from animal models to human patients. Moreover, we review some of the new molecular mechanisms involved in the pathogenesis of pulmonary hypertension, including non-coding RNAs and the application of 'omics' data to understand this pathology, hoping that these new approaches will provide insights to guide the way to personalized diagnosis and treatment.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Healthy mitochondrial function is imperative for most tissues, but especially those with a high e... more Healthy mitochondrial function is imperative for most tissues, but especially those with a high energy demand. Robust evidence linking mitochondrial dysfunction with cardiovascular disease has demonstrated that mitochondrial activity is highly relevant to cardiac muscle performance. Mitochondrial homeostasis is maintained through coordination among the processes that comprise the so-called mitochondrial dynamics machinery. The most-studied elements of cardiac mitochondrial dynamics are mitochondrial fission and fusion, biogenesis and degradation. Selective autophagic removal of mitochondria (mitophagy) is essential for clearing away defective mitochondria but can lead to cell damage and death if not tightly controlled. In cardiovascular cells such as cardiomyocytes and cardiac fibroblasts, mitophagy is involved in metabolic activity, cell differentiation, apoptosis and other physiological processes related to major phenotypic changes. Modulation of mitophagy has detrimental and/or beneficial outcomes in various cardiovascular diseases, suggesting that a deeper understanding of the mechanisms underlying mitochondrial degradation in the heart could provide valuable clinical insights. Here, we discuss current evidence supporting the role of mitophagy in cardiac pathophysiology, with an emphasis on different research models and their interpretations; basic concepts related to this selective autophagy; and the most commonly used experimental approaches for studying this mechanism. Finally, we provide a comprehensive literature analysis on the role of mitophagy in heart failure, ischemia/reperfusion, diabetic cardiomyopathy and other cardiovascular diseases, as well as its potential biomedical applications.
En el modelo preclínico de insuficiencia cardíaca por disfunción sistólica en ratón (coartación d... more En el modelo preclínico de insuficiencia cardíaca por disfunción sistólica en ratón (coartación de aorta torácica) la velocidad de flujo carotídeo determinada precozmente se asocia a función ventricular izquierda tardía
A 51-year-old Hispanic female with no relevant medical history exhibited progressive dyspnoea on ... more A 51-year-old Hispanic female with no relevant medical history exhibited progressive dyspnoea on exertion without haemoptysis, fever, malaise, skin lesions, or arthritis. She denied having oral or genital aphthae, as well as ocular or neurological diseases. Physical examination showed jugular ingurgitation, a wide splitting of the second heart sound, with a loud pulmonary component. Lung auscultation was normal. She had no clubbing or peripheral oedema. Transthoracic echocardiogram revealed severe pulmonary hypertension (PH), with an estimated systolic pulmonary artery pressure of 91 mmHg, and signs of chronic right ventricle pressure overload. Computed tomography angiography revealed pulmonary arteries with severe tortuosity and multiple foci of dilatation and stenosis, showing a ‘string of beads’ appearance, without evidence of pulmonary embolism (Figure 1). There were no lesions either in the carotid or renal arteries, suggestive of fibromuscular dysplasia. Complete blood count, C reactive protein, and sedimentation rate were normal. A serological evaluation for systemic vasculitis and connective tissue diseases was negative.
It is unknown why heart failure progresses even when patients are treated with the best therapy a... more It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.
Hypertension (HTN) is a public health concern and a major preventable cause of cardiovascular dis... more Hypertension (HTN) is a public health concern and a major preventable cause of cardiovascular disease (CVD). When uncontrolled, HTN may lead to adverse cardiac remodeling, left ventricular hypertrophy, and ultimately, heart failure. Regular aerobic exercise training exhibits blood pressure protective effects, improves myocardial function, and may reverse pathologic cardiac hypertrophy. These beneficial effects depend at least partially on improved mitochondrial function, decreased oxidative stress, endothelial dysfunction, and apoptotic cell death, which supports the general recommendation of moderate exercise in CVD patients. However, most of these mechanisms have been described on healthy individuals; the effect of moderate exercise on HTN subjects at a cellular level remain largely unknown. We hypothesized that hypertension in adult spontaneously hypertensive rats (SHRs) reduces the mitochondrial response to moderate exercise in the myocardium. Methods: Eight-month-old SHRs and their normotensive control—Wistar-Kyoto rats (WKYR)—were randomly assigned to moderate exercise on a treadmill five times per week with a running speed set at 10 m/min and 15° inclination. The duration of each session was 45 min with a relative intensity of 70–85% of the maximum O2 consumption for a total of 8 weeks. A control group of untrained animals was maintained in their cages with short sessions of 10 min at 10 m/min two times per week to maintain them accustomed to the treadmill. After completing the exercise protocol, we assessed maximum exercise capacity and echocardiographic parameters. Animals were euthanized, and heart and muscle tissue were harvested for protein determinations and gene expression analysis. Measurements were compared using a nonparametric ANOVA (Kruskal-Wallis), with post-hoc Dunn's test. Results: At baseline, SHR presented myocardial remodeling evidenced by left ventricular hypertrophy (interventricular septum 2.08 ± 0.07 vs. 1.62 ± 0.08 mm, p < 0.001), enlarged left atria (0.62 ± 0.1 mm vs. 0.52 ± 0.1, p = 0.04), and impaired diastolic function (E/A ratio 2.43 ± 0.1 vs. 1.56 ± 0.2) when compared to WKYR. Moderate exercise did not induce changes in ventricular remodeling but improved diastolic filling pattern (E/A ratio 2.43 ± 0.1 in untrained SHR vs. 1.89 ± 0.16 trained SHR, p < 0.01). Histological analysis revealed increased myocyte transversal section area, increased Myh7 (myosin heavy chain 7) expression, and collagen fiber accumulation in SHR-control hearts. While the exercise protocol did not modify cardiac size, there was a significant reduction of cardiomyocyte size in the SHR-exercise group. Conversely, titin expression increased only WYK-exercise animals but remained unchanged in the SHR-exercise group. Mitochondrial response to exercise also diverged between SHR and WYKR: while moderate exercise showed an apparent increase in mRNA levels of Ppargc1α, Opa1, Mfn2, Mff, and Drp1 in WYKR, mitochondrial dynamics proteins remained unchanged in response to exercise in SHR. This finding was further confirmed by decreased levels of MFN2 and OPA1 in SHR at baseline and increased OPA1 processing in response to exercise in heart. In summary, aerobic exercise improves diastolic parameters in SHR but fails to activate the cardiomyocyte mitochondrial adaptive response observed in healthy individuals. This finding may explain the discrepancies on the effect of exercise in clinical settings and evidence of the need to further refine our understanding of the molecular response to physical activity in HTN subjects.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018
Bone integrity depends on a finely tuned balance between bone synthesis by osteoblasts and resorp... more Bone integrity depends on a finely tuned balance between bone synthesis by osteoblasts and resorption by osteoclasts. The secretion capacity of mature osteoblasts requires strict control of proteostasis. Endoplasmic reticulum-associated degradation (ERAD) prevents the accumulation of unfolded ER proteins via dislocation to the cytosol and degradation by the proteasome. The ER membrane protein, homocysteine-inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (HERPUD1), is a key component of the ERAD multiprotein complex which helps to stabilize the complex and facilitate the efficient degradation of unfolded proteins. HERPUD1 expression is strongly up-regulated by the unfolded protein response and cellular stress. The aim of the current study was to establish whether HERPUD1 and ERAD play roles in osteoblast differentiation and maturation. We evaluated preosteoblastic MC3T3-E1 cell and primary rat osteoblast differentiation by measuring calcium deposit levels, alkali...
We report the first optical biosensor for the novel and important cardiac biomarker, galectin-3 (... more We report the first optical biosensor for the novel and important cardiac biomarker, galectin-3 (Gal3), using the anti-Gal3 antibody as a biorecognition element and surface plasmon resonance (SPR) for transducing the bioaffinity event. The immunosensing platform was built at a thiolated Au surface modified by self-assembling four bilayers of poly(diallyldimethylammonium chloride) and graphene oxide (GO), followed by the covalent attachment of 3-aminephenylboronic acid (3ABA). The importance of GO, both as the anchoring point of the antibody and as a field enhancer for improving the biosensor sensitivity, was critically discussed. The advantages of using 3ABA to orientate the anti-Gal3 antibody through the selective link to the Fc region were also demonstrated. The new platform represents an interesting alternative for the label-free biosensing of Gal3 in the whole range of clinically relevant concentrations (linear range between 10.0 and 50.0 ng mL, detection limit of 2.0 ng mL) wit...
Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, ear... more Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, early detection of atherosclerosis, the common pathophysiological mechanism underlying cardiovascular diseases remains elusive, and overt coronary artery disease or myocardial infarction is often the first clinical manifestation. Nanoparticles represent a novel strategy for prevention, diagnosis, and treatment of atherosclerosis, and new multifunctional nanoparticles with combined diagnostic and therapeutic capacities hold the promise for theranostic approaches to this disease. This review focuses on the development of nanosystems for therapy and diagnosis of subclinical atherosclerosis, coronary artery disease, and myocardial infarction and the evolution of nanosystems as theranostic tools. We also discuss the use of nanoparticles in noninvasive imaging, targeted drug delivery, photothermal therapies together with the challenges faced by nanosystems during clinical translation.
Galectin-3 levels in patients hospitalized for decompensated heart failure Background: Galectin-3... more Galectin-3 levels in patients hospitalized for decompensated heart failure Background: Galectin-3 (Gal-3) is a mediator of myocardial fibrosis involved in cardiac remodeling and a potential new prognosis marker in heart failure (HF). Aim: To measure Gal-3 at the moment of discharge in patients hospitalized for HF and its association with different variables. Material and Methods: Patients hospitalized for decompensated HF from four hospitals between August 2014 and March 2015, were included. Demographic, clinical and laboratory variables were recorded at the time of admission. At discharge, a blood sample was withdrawn to measure Gal-3 and brain natriuretic propeptide (Pro-BNP). Patients were separated in two groups, according to the level of Gal-3 (using a cutoff value of 17.8 ng/mL), comparing clinical and laboratory values between groups. Results: We included 52 patients with HF aged 70 ± 17 years (42% females).
Increased inflammation biomarkers plasma levels, including C-reactive protein (CRP), have been as... more Increased inflammation biomarkers plasma levels, including C-reactive protein (CRP), have been associated with the initiation and perpetuation of atrial fibrillation (AF). However, it is not known whether an increased CRP plasma level, without concomitant inflammation, is sufficient to induce AF. We investigated whether higher CRP plasma levels, determined by the presence of +219G>A CRP gene polymorphism, is associated with an increased risk of post-operative AF. One hundred and fifteen adult patients submitted to elective coronary surgery were genotyped for the CRP +219G>A polymorphism. CRP plasma levels were determined by enzyme-linked immunosorbent assay. CRP plasma levels before surgery were higher in GG than in GA+AA patients (3.4±3.1 vs. 1.7±1.8, p<0.015). Thirteen percent of the patients presented post-operative AF. Despite the positive correlation between the polymorphism and CRP levels, there was no significant difference in the occurrence of post-operative AF betw...
luis sepúlVeDa 7 en representación del grupo iCaro Frailty in patients admitted to hospital with ... more luis sepúlVeDa 7 en representación del grupo iCaro Frailty in patients admitted to hospital with acute decompensated heart failure Background: Frailty is a geriatric syndrome characterized by a progressive impairment in the subjects' ability to respond to environmental stress. Frailty is more commonly found in heart failure (HF) patients than in general population and it is an independent predictor of rehospitalization, emergency room visits and death. Aim: To estimate the prevalence of frailty in patients with decompensated HF admitted to four hospitals in Santiago, Chile. Material and Methods: Cross-sectional study. Subjects aged 60 or older consecutively admitted for decompensated HF to the study centers between August 2014 and March 2015 were included. Frailty was defined as the presence of three or more of the following criteria: unintended weight loss, muscular weakness, depression symptoms (exhaustion), reduced gait speed and low physical activity. Independent variables were tested for association using simple logistic regression. Variables associated with frailty (p < 0.05) were included in a multiple logistic regression model. Results: Seventy-nine subjects were included. The prevalence of frailty was 50.6%. Frail patients were mostly female (52.6%) and older than non-frail subjects (73.
Right atrium function and ventricular function have significant prognostic value in pulmonary art... more Right atrium function and ventricular function have significant prognostic value in pulmonary arterial hypertension patients. Acute changes in right ventricular synchrony and right atrium function postiloprost inhalation have not been evaluated. Cross-sectional study. Consecutive pulmonary arterial hypertension patients (group I from Nice classification) were included. Echocardiographic right atrium and right ventricular function pre- and postiloprost inhalation, including a right ventricular dyssynchrony index and right atrium function using speckle tracking, were performed in all patients. Twenty pulmonary arterial hypertension patients, 44±7 years and 90% females, were included. After iloprost inhalation, we observed a significant increment in right ventricular fractional area change and a significant decrease in right ventricular dyssynchrony index (21.4±5.6% vs 26.1±4.0 %, P=.007 and 79±44 vs 32±22 mseconds, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.01, respectively), also an improvement in right atrium reservoir function (8.6±3.1% vs 11.7±3.5 %, P=.002). Iloprost inhalation induces acute changes in right ventricular function, dyssynchrony, and right atrium performance that may add relevant clinical information in the management and risk stratification of pulmonary arterial hypertension patients.
Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary ... more Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary vasodilator therapies Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Long-term survival remains poor despite of advances in specific vasodilator therapy. Aim: To describe the survival rate in a cohort of PAH patients in two referral centers in Chile. Patients and Methods: One hundred fifteen patients aged 43 ± 15.6 years (85% females) with PAH qualified for this study. Their median pulmonary artery pressure was 55.4 ± 14 mmHg and their six minutes walking capacity was 368 ± 119 m. They were followed for 58 ± 0.4 months and their actual survival rates were compared with the estimated survival using the equation proposed by the French registry of PAH. Results: One, two and three year survival rates were 97, 94 and 89%, respectively. The observed survival rates were greater than the estimated survival. Conclusions: The improvement in survival rates observed in this cohort of patients is similar to what has been described in literature.
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