Papers by David Cruz-Robles
Nutrition, 2014
Early endothelial nitrosylation and increased abdominal adiposity after long-term consumption of ... more Early endothelial nitrosylation and increased abdominal adiposity after long-term consumption of frying used canola oil in Wistar rats
Resumen La infl amacion tiene un papel importante en las lesiones ateroscleroticas, ya que afecta... more Resumen La infl amacion tiene un papel importante en las lesiones ateroscleroticas, ya que afecta a diver-sos estados del desarrollo del ateroma, que van desde el reclutamiento inicial de leucocitos hasta la rotura de la placa aterosclerotica inestable. Las reacciones infl amatorias en las placas ateroscleroticas coronarias son determinantes en el curso clinico de los pacientes con sindrome coronario agudo y enfermedad arterial coronaria. Estudios recientes sugieren que varias mo-leculas inflamatorias, que se generan en diferentes puntos del desarrollo de sindrome isquemico coronario agudo, pueden refl ejar diferentes aspectos del proceso aterotrombotico. Dichas mo-leculas pueden tener un papel en el riesgo a desarrollar enfermedad arterial coronaria y pueden correlacionarse con la gravedad de esta. Algunas citocinas, proteinas de fase aguda, moleculas de adhesion y otras moleculas, que son liberadas por las celulas infl amatorias, pueden refl ejar los procesos infl amatorios en las...
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2020
It has been proposed that the cardiovascular effects of obesity are related to epicardial adipose... more It has been proposed that the cardiovascular effects of obesity are related to epicardial adipose tissue (EAT), which seems to play an active role on the development and calcification of atherosclerotic plaques, but the mechanisms are still unknown. Therefore, the aim of this study was to determine whether the EAT expresses the genes of calcifying factors and whether such expression is associated with the body mass index (BMI) and with the presence of coronary artery calcium (CAC) in patients with coronary artery disease (CAD). Patients and Methods: Forty-three patients with CAD were enrolled specifically for this study, and their CAC score and EAT volume were determined by computed tomography. As the group of comparison, 41 patients with aortic valve stenosis and CAC = 0 were included (control group). A representative subgroup of 16 CAD patients and 23 controls were selected to obtain EAT biopsies during the chirurgical procedure from the atrio-interventricular groove. The mRNA expression of bone morphogenetic protein-2 and -4 (BMP-2, BMP-4), osteopontin (OPN), osteonectin (ON), and osteoprotegerin (OPG) in EAT was determined by qPCR. Results: The gene expression of OPN and BMP-2 was 70% and 52% higher in the EAT from CAD patients than that in controls, respectively, whereas the expression of OPG, ON, and BMP-4 was similar in both groups. The EAT volume positively correlated with OPG and with the BMI, suggesting a relationship of obesity with local higher expression of calcifying genes in the coronary territory. The logistic regression analysis showed that high levels of both OPN and BMP-2 increased about 6 and 8 times the odds of coronary calcification (CAC score > 0), respectively. Conclusion: EAT correlated with BMI and expressed the mRNA of calcifying genes but only OPN and BMP-2 expression was higher in CAD patients. Higher levels of both OPN and BMP-2 statistically determined the presence of calcium in coronary arteries of CAD patients.
Annals of parasitology
The clinical manifestations of human Chagas disease are associated with several factors, includin... more The clinical manifestations of human Chagas disease are associated with several factors, including immunological alterations, in this regard, many studies propose that tissue damage might be more severe in the absence of immune regulatory mechanisms, other factors are the genetic background of host and parasite. Trypanosoma cruzi population is genetically, biochemistry and pathogenic diverse along the Latin-America continent and phylogenetic ally are divided into six intra-species lineages TcI-VI. The TcI lineage has a wide distribution with heterogeneous virulence and pathogenesis within strains. In Mexico, the main circulating lineage is TcI in human infections. We analyzed intracytoplasmic cytokines of unstimulated peripheral T lymphocytes, and the level of cytokines (IL-2, IL-4, IL-12, IL-10, IFN-γ and sIL-2R) in the serum of Mexican chagasic subjects. The population studied consisted of 15 asymptomatic individuals, 17 patients with chronic chagasic cardiopathy (CCC), 20 patient...
Lipids in Health and Disease, 2017
Background: Previous studies suggest a relationship of the epicardial adipose tissue (EAT) with p... more Background: Previous studies suggest a relationship of the epicardial adipose tissue (EAT) with progression and calcification of the atherosclerotic plaque; however, it is unknown if this tissue expresses genes that may participate on these processes and if the expression of these genes is regulated by high-density lipoprotein (HDL) subclasses. Methods: To explore this possibility, we determined the mRNA expression by qPCR of a pro-calcifying gene (osteopontin (OPN)), and two anti-calcifying genes (osteoprotegerin (OPG) and osteonectin (ON)), in biopsies of EAT obtained from 15 patients with coronary artery disease (CAD) determined by angiography, and 15 patients with diagnostic of aortic valve stenosis but without CAD as control group. We determined the distribution and composition of HDL subclasses by electrophoresis and their statistical relationship with the gene expression in EAT. Results: EAT from CAD patients showed a higher expression level of OPN and OPG than control group, whereas ON expression was similar between groups. Large HDL subclasses were cholesterol-poor in CAD patients as estimated by the cholesterol-to-phospholipid ratio. A linear regression model showed an independent association of OPN expression with HDL3a-cholesterol, and OPG expression with the relative proportion of HDL3b protein. Logistic analysis determined that OPN expression was positively associated with the presence of atherosclerotic plaque Conclusion: OPN, ON, and OPG genes are transcribed in EAT; to the exception of ON, the level of expression was different in CAD patients and control group, and correlated with some HDL subclasses, suggesting a new role of these lipoproteins.
Cardiology Research and Practice, 2016
Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinic... more Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients.Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD.Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 μg/L versus 20.81 μg/L,p=0.002) and homocysteine (11.36μmol/L versus 8.81μmol/L,p<0.01) compared to the patients without significant CAD. Specifically, in patients with...
The Journal of Molecular Diagnostics, 2015
An international study was performed by 26 experienced PCR laboratories from 14 countries to asse... more An international study was performed by 26 experienced PCR laboratories from 14 countries to assess the performance of duplex quantitative real-time PCR (qPCR) strategies on the basis of TaqMan probes for detection and quantification of parasitic loads in peripheral blood samples from Chagas disease patients. Two methods were studied: Satellite DNA (SatDNA) qPCR and kinetoplastid DNA (kDNA) qPCR. Both methods included an internal amplification control. Reportable range, analytical sensitivity, limits of detection and quantification, and precision were estimated according to international guidelines. In addition, inclusivity and exclusivity were estimated with DNA from stocks representing the different Trypanosoma cruzi discrete typing units and Trypanosoma rangeli and Leishmania spp. Both methods were challenged against 156 blood samples provided by the participant laboratories, including samples from acute and chronic patients with varied clinical findings, infected by oral route or vectorial transmission. kDNA qPCR showed better analytical sensitivity than SatDNA qPCR with limits of detection of 0.23 and 0.70 parasite equivalents/mL, respectively. Analyses of clinical samples revealed a high concordance in terms of sensitivity and parasitic loads determined by both SatDNA and kDNA qPCRs. This effort is a major step toward international validation of qPCR methods for the quantification of T. cruzi DNA in human blood samples, aiming to provide an accurate surrogate biomarker for diagnosis and treatment monitoring for patients with Chagas disease.
Archivos de cardiología de México
A novel SCN5A mutation was found in a child with congenital sick sinus disease, a Brugadalike el... more A novel SCN5A mutation was found in a child with congenital sick sinus disease, a Brugadalike electrocardiogram and recurrent aborted sudden death. The mutation (L1821fs/10) is a 4 base pair deletion (TCTG) at position 54645467 in exon 28 of the gene. The novel mutation is predicted to produce a frameshift leading to a premature stop codon after ten missense amino acids upstream that did not allow the generation of the complete protein, and probably producing an incomplete and therefore non functional protein. The resulting alteration in sodium current could explain the clinical phenotype observed in this patient.
Phytotherapy Research, 2015
Serenoa repens has been widely used to treat benign prostatic hyperplasia and lower urinary tract... more Serenoa repens has been widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms; however, most of the studies have been conducted in individuals with normal weight and not obese. In this study, the effects of a lipidic extract of S. repens, in markers of oxidative stress, inflammation, and growth factors, in obese rats with testosterone-induced prostatic hyperplasia, were investigated. Total nitrites, malondialdehyde, total glutathione, superoxide dismutase (SOD), and catalase activity were measured; in addition, assays for inflammatory cytokines TNF-α, IL-1β, IL-6 and the growth factors basic fibroblast growth factor (FGFb) and vascular endothelial growth factor (VEGF) were performed. The obese rats had a higher prostate weight compared with controls. S. repens significantly decreased prostate weight, total nitrites, and malondialdehyde; improved total glutathione, SOD, and catalase activity; and significantly reduced inflammatory (TNF-α, IL-1β and IL-6) and growth factors (VEGF and FGFb). S. repens showed high antioxidant and antiinflammatory activity in obese rats, suggesting that their use could be beneficial in the treatment of benign prostatic hyperplasia.
Experimental and Molecular Pathology, 2015
The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as suscep... more The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as susceptibility markers for coronary artery disease (CAD) and/or restenosis after coronary stent placement in a group of Mexican patients. Five polymorphisms of the AGT (rs699, rs4762, rs5051, rs5049, rs5046) and two of the REN (rs5707, rs5705) genes were analyzed by 5&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;#39; exonuclease TaqMan genotyping assays in 240 patients with CAD who underwent coronary artery stenting (76 with restenosis and 164 without restenosis). A group of 610 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. The results showed that the distribution of AGT and REN polymorphisms were similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant, heterozygous and additive models, the REN A4280C (rs5705) polymorphism was associated with increased risk of CAD (OR=1.76, PCo-dom=0.006, OR=1.81, PDom=0.001, OR=1.75, PHet=0.003 and OR=1.59, PAdd=0.003, respectively). All models were adjusted for age, gender, diabetes, dyslipidemia, hypertension and smoking habit. The TC haplotype of the REN gene was associated with increased risk of CAD (OR=1.53, P=0.014). The data suggest that the REN C4280A (rs5705) polymorphism plays an important role in the risk of developing CAD with the highest risk for C allele, but do not support its role as a risk factor for developing restenosis after coronary stenting.
![Research paper thumbnail of [Pro-inflammatory and anti-inflammatory markers in coronary artery disease and acute ischemic coronary syndrome]](https://attachments.academia-assets.com/85780822/thumbnails/1.jpg)
Archivos de cardiología de México
Inflammation plays an important role in the development of atherosclerotic lesions, affecting sev... more Inflammation plays an important role in the development of atherosclerotic lesions, affecting several stages of the atheroma's development going from the initial leukocyte recruitment to the eventual rupture of the unstable atherosclerotic plaque. The inflammatory reactions within coronary atherosclerotic plaques influence the clinical outcome of acute coronary syndromes and coronary artery disease. Recent studies suggest that inflammation markers may reflect different aspects of the atherothrombotic process in relation to the stages of acute coronary syndrome. These markers play an important role in the risk of developing coronary artery disease, and may correlate with its severity. Some cytokines, acute phase proteins, acute phase reactants proteins, and adhesion molecules released from the inflammatory cells may reflect the inflammatory process in atherosclerotic plaques. However, it remains to be determined whether these pro- and anti-inflammation markers may confer risk or ...
Archivos de cardiología de México
In this work it is emphasized the presence of the fibrinolitico system in different physiological... more In this work it is emphasized the presence of the fibrinolitico system in different physiological mechanisms, specially in the antithrombotic regulation of the hemostasis. It is described: the mechanism of activation of plasminogen by their activators as much on the fibrin as in the cells surface; the inhibition of the activators in different metabolic alterations.
Archivos de cardiología de México
A novel SCN5A mutation was found in a child with congenital sick sinus disease, a Brugada-like el... more A novel SCN5A mutation was found in a child with congenital sick sinus disease, a Brugada-like electrocardiogram and recurrent aborted sudden death. The mutation (L1821fs/10) is a 4 base pair deletion (TCTG) at position 5464-5467 in exon 28 of the gene. The novel mutation is predicted to produce a frameshift leading to a premature stop codon after ten missense amino acids upstream that did not allow the generation of the complete protein, and probably producing an incomplete and therefore non functional protein. The resulting alteration in sodium current could explain the clinical phenotype observed in this patient.
![Research paper thumbnail of [Genetics and molecular biology of the congenital, and acquired heart disease]](https://attachments.academia-assets.com/85780659/thumbnails/1.jpg)
Archivos de cardiología de México
The heart is the first organ to form and function in the embryo, and all subsequent events in the... more The heart is the first organ to form and function in the embryo, and all subsequent events in the life of the organism depend on the heart's ability to match its output with the organism's demands for oxygen and nutrients. Abnormalities in heart formation, the most common form of human birth defects, afflict nearly 1% of newborns, and their frequency in spontaneously aborted pregnancies is estimated to be tenfold higher. With the completion of the sequencing of the human genome, molecular genetic efforts directed at finding genes for monogenic traits have accelerated dramatically. Breakthroughs in molecular genetic technology have just begun to be applied in pediatric cardiology stemming from the use of chromosomal mapping and the identification of genes involved in both the primary etiology and as significant risk factors in the development of cardiac and vascular abnormalities. This review will focus on information provided by molecular and genetic analysis in the diagnosi...
Archivos de Cardiología de México, 2015
Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from altera... more Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City.
Molecular Immunology, 2008
We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals)... more We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals) to directly obtain the HLA-A/B/DRB1/DQB1 haplotypes and their linkage disequilibrium (LD). The most frequent HLA haplotypes observed were: A*02-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*04-DQB1*0302, A*68-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*08-DQB1*04, A*33-B*1402-DRB1*01-DQB1*05, and A*24-B*35-DRB1*04-DQB1*0302. The four most common haplotypes found by our study involve those previously reported in Amerindian populations. LD analysis of HLA-A-B and HLA-B-DRB1 loci showed significant associations between A29(19)-B44(12), A33(19)-B65(14), A1-B8, A26(19)-B44(12), A24(9)-B61(40), B65(14)-DR1, B8-DR17(3), B44(12)-DR7, B7-DR15(2), and B39(16)-DR4. Also, all DRB1-DQB1 associations showed significant LD values. Admixture estimations using a trihybrid model showed that Mexicans from the State of Sinaloa (Northern Mexico) have a greater proportion of European genetic component compared with Mexicans from the Central area of Mexico, who have a greater percentage of Amerindian genes. Our results are important for future comparative genetic studies of different Mexican ethnic groups with special relevance to disease association and transplantation studies.
Life Sciences, 1999
In the it1 viw rat heart model with transient (5 min) regional ischemia, as induced by left coron... more In the it1 viw rat heart model with transient (5 min) regional ischemia, as induced by left coronary artery ligation, we have demonstrated that perezone reduces dramatically the incidence of reperfusion-induced-arrhythmias. Administered 5 minutes before coronary occlusion, at a dose of 3. I mg/kg, this drug effectively protects against the high incidence of arrhythmias and the fall of blood pressure. In addition, it inhibits the release of lactic dehydrogenase and creatine-kinase enzymes to the plasma. We propose that the protective effect of perezone might be related to its well documented action of promoting the release of intramitochondrial Ca 2+, thus, maintaining ATP production during reperfusion.
Clinica Chimica Acta, 2007
Background: HDL becomes enriched with non-esterified fatty acids (NEFAs) in some pathologies, suc... more Background: HDL becomes enriched with non-esterified fatty acids (NEFAs) in some pathologies, such as nephrotic syndrome, as well as after aerobic exercise. However, little is known about the impact of NEFAs on HDL metabolism. We investigated the effects of one NEFA, the palmitic acid, on HDL structure and catabolism. Methods: HDL enrichment with palmitic acid (HDL Pal) was performed by fusing phosphatidyl choline small unilamellar vesicles containing the NEFA with human HDL isolated from a pool of 5 normolipidemic plasma. HDL enriched only with phosphatidyl choline (HDL Phl) and native HDL (HDL Ctrl) were included as controls. Results: As expected, HDL Pal surface charge density was higher than HDL Phl and HDL Ctrl (2014.4 ± 164.8 vs. 1682.7 ± 149.5 and 1758.2 ± 124.3esu/cm 2 , respectively, p b 0.05). Both, HDL Pal and HDL Phl were better substrates for cholesteryl esters transfer protein (CETP) than HDL Ctrl (% of transfer, 13.02 ± 3.8 and 12.7 ± 4.5 vs. 7.8 ± 2.7% in 16 h, respectively, p b 0.05). HDL Pal apo A-I catabolism in vivo, as performed in New Zealand white rabbits by exogenous radiolabeling, was markedly lower than that of HDL Phl and HDL Ctrl (fractional catabolic rate, 0.019 ± 0.008 vs. 0.030 ± 0.005 and 0.047 ± 0.003 h − 1 , respectively, p b 0.001), suggesting that negative charge is inversely related to HDL-apo A-I catabolism. Conclusions: Enrichment with palmitic acid increases the negative electric charge of HDL at physiological pH, contributes to decrease their catabolism, and is associated to an enhanced lipid transfer by CETP that has been related to the atherogenic process.
Clinica Chimica Acta, 2011
The antiatherogenic role of different HDL subclasses is still controversial. HDL particles of the... more The antiatherogenic role of different HDL subclasses is still controversial. HDL particles of the same size can have different lipid contents in some physiopathological situations. However, little is known about the plasma lipid levels of HDL subclasses when they are separated by their hydrodynamic diameter. Triglycerides (Tg), phosphatidylcholine (Ph), and cholesterol (C) plasma concentrations of HDL subclasses, were determined by enzymatic staining on polyacrylamide gradient gel (PAGE) in 50 pediatric patients with metabolic syndrome (MS), and 50 control children paired by age and gender. Proteins of HDL subclasses were also stained for the assessment of the relative size distribution of HDL. Relative HDL size distribution was shifted to small particles in MS pediatric patients when determined per protein. In contrast, cholesterol plasma concentrations corresponding to the HDL2b, 2a, 3a, and 3b subclasses were decreased; triglycerides of HDL3b and 3c, as well as plasma phospholipids from HDL3c, were elevated in MS patients as compared to controls. The C-to-Ph ratio, considered as indicative of HDL composition, was similar among the 5 HDL subclasses in control subjects, whereas this ratio gradually decreased from large HDL2b to small HDL3c in the MS group. Cholesterol plasma concentrations of HDL subclasses correlated with the components of the MS. Lipids of HDL subclasses provide more and accurate information than the relative HDL size distribution determined by protein staining, and may contribute to understand better HDL metabolism and the coronary risk associated to these lipoproteins.
… de cardiología de …, 2005
Resumen El corazón es el primer órgano que se forma y funciona en el embrión, de tal suerte que t... more Resumen El corazón es el primer órgano que se forma y funciona en el embrión, de tal suerte que todos los eventos subsecuentes en la vida del organismo dependen de la habilidad de este órgano para atender las demandas de oxígeno y nutrientes que éste ...
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Papers by David Cruz-Robles