ATR1 A1166C (rs5186), FII G20210A (rs1799963), FV G1691A (rs6025), FXIII 97G > T (rs11466016) and MTHFR A1298C (rs1801131) polymorphisms and the risk of ST-elevation myocardial infarction in young Mexican individuals.

BACKGROUND: Previous studies had identified genetic variants associated with Myocardial Infarction, but results are inconclusive. We examined the association between FII G20210A (rs1799963), FV G1691A (rs6025), FXIII 97G > T (rs11466016), ATR1 A1166C (rs5186) and MTHFR A1298C (rs1801131) polymorphisms and ST elevation Myocardial Infarction in young Mexican individuals. METHODS: We included a total of 350 patients with Myocardial Infarction <45 years old and 350 controls matched by age and gender. The polymorphisms were analyzed by PCR-RFLP using specific restriction enzymes. DNA fragments were separated by electrophoresis in 2% gel of agarose and visualized using SYBR green. RESULTS: The A1166C (p = 0.004) but not FXIII 97G > T (p = 0.19), G20210A (p = 0.32), G1691A (p = No significant) and A1298C (p = 0.21) polymorphisms were associated with increased risk for ST elevation Myocardial Infarction. Moreover, dyslipidemia, hypertension, smoking and family history of atherothrombotic disease were associated. CONCLUSIONS: We found that A1166C represented increased risk for ST elevation Myocardial Infarction. However, G20210A, G1691A, 97G > T, and A1298C were not associated. In addition, we had determined that Glu298Asp, PLA1/A2, TAFI Thr325Ile, ACE I/D, AGT M235T and PAI-1 4G/5G polymorphisms represented increased risk in the same group of patients. However, MTHFR C677T, AGT T174M, FV G1691A, TSP-1 N700S, MTHFR C677T and TAFI 174 M polymorphisms were no associated. Our results suggest that in young patients with ST Myocardial Infarction, those polymorphisms could contribute to premature endothelial dysfunction, atherothrombosis, vasoconstriction, increased platelet aggregation, muscle cell migration and proliferation. Further studies are required to try to better assess gene-gene and gene-modifiable factors interaction.

The role of Vav3 expression for inflammation and cell death during experimental myocardial infarction.

OBJECTIVES: Myocardial Infarction (MI) is the leading cause of chronic heart failure. Previous studies have suggested that Vav3, a receptor protein tyrosine kinase signal transducer, is associated with a variety of cellular signaling processes such as cell morphology regulation and cell transformation with oncogenic activity. However, the mechanism of Vav3-mediated MI development requires further investigation. METHOD: Here, The authors established an MI rat model by ligating the anterior descending branch of the left coronary artery, and an MI cell model by treating cardiomyocytes with H2O2. Microarray analysis was conducted to identify genes with differential expression in heart tissues relevant to MI occurrence and development. Vav3 was thus selected for further investigation. RESULTS: Vav3 downregulation was observed in MI heart tissue and H2O2-treated cardiomyocytes. Administration of Lentiviral Vav3 (LV-VAV3) in MI rats upregulated Vav3 expression in MI heart tissue. Restoration of Vav3 expression reduced infarct area and ameliorated cardiac function in MI rats. Cardiac inflammation, apoptosis, and upregulation of NFκB signal in heart tissue of MI animals were assessed using ELISA, TUNEL staining, real-time PCR, and WB. Vav3 overexpression reduced cardiac inflammation and apoptosis and inhibited NFκB expression and activation. Betulinic Acid (BA) was then used to re-activate NFκB in Vav3-overexpressed and H2O2-induced cardiomyocytes. The expression of P50 and P65, as well as nuclear P65, was significantly increased by BA exposure. CONCLUSIONS: Vav3 might serve as a target to reduce ischemia damage by suppressing the inflammation and apoptosis of cardiomyocytes.

TREML4 polymorphisms increase the mRNA in blood leukocytes in the progression of atherosclerosis.

TREML4 and other members of the triggering receptor expressed in the myeloid cell family are associated with a risk of atherosclerosis and progression in coronary artery disease, acute coronary syndrome, and coronary artery calcification. Herein, the relationship between TREML4 expression and its polymorphisms (rs2803495 and rs280396) was evaluated in patients with subclinical atherosclerosis (n = 340) and heart failure post-acute myocardial infarction (MI) (n = 68) for the first time. TREML4 variants rs2803495 (A > G) and rs2803496 (T > C) and leukocyte mRNA expression was analyzed by qRT-PCR. The rs2803495 G allele was associated with TREML4 expression (OR 8.01, CI 3.78-16.99, p < 0.001). Patients carrying the rs2803496 C minor allele (TC/CC genotypes) were more likely to express TREML4 than those without the C allele (OR 10.42, CI 4.76-22.78, p < 0.001), as well as having higher levels of TREML4 expression (OR 4.88, CI 2.35-10.12, p < 0.001). Thus, we report for the first time that TREML4 is not associated with the early stages of atherosclerotic plaque formation and later stages after MI. In conclusion, TREML4 mRNA expression in blood leukocytes is influenced by minor alleles (G and C) and may regulate differently during the atherosclerosis progression stages, but not in asymptomatic atherosclerosis disease and post-MI.

Multicellular regulation of miR-196a-5p and miR-425-5 from adipose stem cell-derived exosomes and cardiac repair.

Cardiac transplantation of adipose-derived stem cells (ASC) modulates the post-myocardial infarction (post-MI) repair response. Biomolecules secreted or shuttled within extracellular vesicles, such as exosomes, may participate in the concerted response. We investigated the exosome's microRNAs due to their capacity to fine-tune gene expression, potentially affecting the multicellular repair response. We profiled and quantified rat ASC-exosome miRNAs and used bioinformatics to select uncharacterized miRNAs down-regulated in post-MI related to cardiac repair. We selected and validated miR-196a-5p and miR-425-5p as candidates for the concerted response in neonatal cardiomyocytes, cardiac fibroblasts, endothelial cells, and macrophages using a high-content screening platform. Both miRNAs prevented cardiomyocyte ischemia-induced mitochondrial dysfunction and reactive oxygen species production, increased angiogenesis, and polarized macrophages toward the anti-inflammatory M2 immunophenotype. Moreover, miR-196a-5p reduced and reversed myofibroblast activation and decreased collagen expression. Our data provide evidence that the exosome-derived miR-196a-5p and miR-425-5p influence biological processes critical to the concerted multicellular repair response post-MI.

Role of apolipoprotein O in autophagy via the p38 mitogen-activated protein kinase signaling pathway in myocardial infarction.

OBJECTIVE: To explore the role and possible mechanisms of action of apolipoprotein O (APOO) in autophagy in Myocardial Infarction (MI) in vivo and in vitro. METHODS: Differential gene expression and single Gene Set Enrichment Analysis (GSEA) were used to evaluate MI-related candidate genes. Animal and cell MI models were established. Sh-APOO, si-APOO, and SB203580 were used to inhibit the expression of APOO or p38MAPK. Western blot and qRT-PCR were used to analyze the expression levels of the target protein or mRNA. Apoptosis was observed using the TUNEL assay. The plasma concentrations of CK-MB and cTn-I in humans and mice were determined. RESULTS: In the GSE23294 dataset, APOO mRNA was highly expressed in the left ventricle of mice with MI; GSEA revealed that APOO was positively correlated with p38MAPK, autophagy, and apoptosis. The plasma concentration of APOO in patients with MI was significantly higher than that in healthy subjects. The expression of APOO, Beclin-1, LC3, and Bax in mouse and AC16 cell MI models increased, while the level of Bcl-2 decreased. After silencing the APOO gene, the expression of APOO was downregulated; meanwhile, changes in autophagy, apoptosis and myocardial cell injury were reversed in vivo and in vitro. Furthermore, autophagy was alleviated after AC16 cells were treated with SB203580. CONCLUSIONS: The increased APOO expression in mouse and cell MI models may activate autophagy and apoptosis by regulating the p38MAPK signaling pathway, thus aggravating the myocardial injury.

Photobiomodulation therapy's effects on cardiac fibrosis activation after experimental myocardial infarction.

INTRODUCTION: Ischemic heart disease is the leading cause of death worldwide, and interventions to reduce myocardial infarction (MI) complications are widely researched. Photobiomodulation therapy (PBMT) has altered multiple biological processes in tissues and organs, including the heart. OBJECTIVES: This study aimed to assess the temporal effects of PBMT on cardiac fibrosis activation after MI in rats. In this proof-of-concept study, we monitored the change in expression patterns over time of genes and microRNAs (miRNAs) involved in the formation of cardiac fibrosis post-MI submitted to PBMT. MATERIALS AND METHODS: Experimental MI was induced, and PBMT was applied shortly after coronary artery ligation (laser light of wavelength 660 nm, 15 mW of power, energy density 22.5 J/cm2 , 60 seconds of application, irradiated area 0.785 cm2 , fluence 1.1 J/cm2 ). Ventricular septal samples were collected at 30 minutes, 3, 6, 24 hours, and 3 days post-MI to determine temporal PBMT's effects on messenger RNA (mRNA) expression associated with cardiac fibrosis activation and miRNAs expression. RESULTS: PBMT, when applied after ischemia, reversed the changes in mRNA expression of myocardial extracellular matrix genes induced by MI. Surprisingly, PBMT modified cardiac miRNAs expression related to fibrosis replacement in the myocardium. Expression correlations between myocardial mRNAs were assessed. The correlation coefficient between miRNAs and target mRNAs was also determined. A positive correlation was detected among miR-21 and transforming growth factor beta-1 mRNA. The miR-29a expression negatively correlated to Col1a1, Col3a1, and MMP-2 mRNA expressions. In addition, we observed that miR-133 and Col1a1 mRNA were negatively correlated. CONCLUSION: The results suggest that PBMT, through the modulation of gene transcription and miRNA expressions, can interfere in cardiac fibrosis activation after MI, mainly reversing the signaling pathway of profibrotic genes.

Triatriatum sinistrum em adulto assintomático: relato de caso / Cor triatriatum sinistrum in an asymptomatic adult: a case report

Cor triatriatum é um anomalia cardíaca congênita rara frequentemente diagnosticada na primeira infância. Este estudo de caso apresenta um adulto com um achado acidental de cor triatriatum sinistrum. Com base na apresentação clínica, o paciente foi tratado de forma conservadora. São apresentados achados de imagens ecocardiográficas de cor triatriatum sinistrum deste paciente juntamente de revisão narrativa da literatura sobre essa doença.(AU)

Cor triatriatum is a rare congenital heart anomaly often diagnosed in early childhood. This case study features an adult with an incidental finding of cor triatriatum sinistrum. Based on the clinical presentation, the patient was treated conservatively. Cor triatriatum sinistrum echocardiographic image findings of this patient are presented along with a narrative review of the literature about this disease. (AU)

Exercise Testing, Family History, and Subclinical Atherosclerosis Markers for Cardiovascular Risk Reclassification in Middle-Aged Women

Abstract Background Cardiovascular diseases are the main cause of death in women and the accuracy of currently available risk scores is questionable. Objective To reclassify the risk estimated by the Framingham Risk Score (FRS) in asymptomatic middle-aged women by incorporating family history, exercise testing variables, and subclinical atherosclerosis markers. Methods This cross-sectional study included 509 women (age range, 46-65 years) without cardiovascular symptoms. Those at low or intermediate risk by the FRS were reclassified to a higher level considering premature family history of acute myocardial infarction and/or sudden death; four variables from exercise testing; and two variables related to subclinical atherosclerosis markers. The homogeneity of these variables according to the FRS was verified by Pearson chi-square test (p<0.05). Results According to the FRS, 80.2%, 6.2%, and 13.6% of the women were classified as low (<5%), intermediate (5-10%), and high (>10%) risks, respectively. The intermediate-risk stratum showed the highest increase (from 6.2% to 33.3%) with addition of family history; followed by addition of chronotropic index <80% (to 24.2%); functional capacity <85% (22.2%), coronary calcium score >0 (20.6%); decreased one-minute heart rate recovery ≤12 bpm (15.2%); carotid intima-media thickness >1 mm and/or carotid plaque (13.8%) and ST-segment depression (9.0%). The high-risk stratum increased to 14.4% with the addition of reduced heart rate recovery and to 17.1% with the coronary calcium score. Conclusion Incorporation of premature family history of cardiovascular events, exercise testing abnormal parameters, and subclinical atherosclerosis markers into the FRS led to risk reclassification in 3.0-29.7% of asymptomatic middle-aged women, mainly by an increase from low to intermediate risk.

Photobiomodulation Therapy on Myocardial Infarction in Rats: Transcriptional and Posttranscriptional Implications to Cardiac Remodeling.

BACKGROUND AND OBJECTIVES: Induction of myocardial infarction (MI) in rats by occlusion of the left anterior descending coronary artery is an experimental model used in research to elucidate functional, structural, and molecular modifications associated with ischemic heart disease. Photobiomodulation therapy (PBMT) has become a therapeutic alternative by modulating various biological processes eliciting several effects, including anti-inflammatory and pro-proliferative actions. The main objective of this work was to evaluate the effect of PBMT in the modulation of transcriptional and post-transcriptional changes that occurred in myocardium signal transduction pathways after MI. STUDY DESIGN/MATERIALS AND METHODS: Continuous wave (CW) non-thermal laser parameters were: 660 nm wavelength, power 15 mW, with a total energy of 0.9 J, fluence of 1.15 J/cm2 , spot size of 0.785 cm2 , and time of 60 seconds. Using in silico analysis, we selected and then, quantified the expression of messenger RNA (mRNA) of 47 genes of 9 signaling pathways associated with MI (angiogenesis, cell survival, hypertrophy, oxidative stress, apoptosis, extracellular matrix, calcium kinetics, cell metabolism, and inflammation). Messenger RNA expression quantification was performed in myocardial samples by polymerase chain reaction real-time array using TaqMan customized plates. RESULTS: Our results evidenced that MI modified mRNA expression of several well-known biomarkers related to detrimental cardiac activity in almost all signaling pathways analyzed. However, PBMT reverted most of these transcriptional changes. More expressively, PBMT provoked a robust decrease in mRNA expression of molecules that participate in post-MI inflammation and ECM composition, such as IL-6, TNF receptor, TGFb1, and collagen I and III. Global microRNA (miRNA) expression analysis revealed that PBMT decreased miR-221, miR-34c, and miR-93 expressions post-MI, which are related to deleterious effects in cardiac remodeling. CONCLUSION: Thus, the identification of transcriptional and post-transcriptional changes induced by PBMT may be used to interfere in the molecular dynamics of cardiac remodeling post-MI.

Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction.

Estrogen receptors (ER) mediate functions beyond their endocrine roles, as modulation of cardiovascular, renal, and immune systems through anti-inflammatory and anti-apoptotic effects, preventing necrosis of cardiomyocytes and endothelial cells, and attenuating cardiac hypertrophy. Estradiol (E2) prevents cardiac dysfunction, increases nitric oxide synthesis, and reduces the proliferation of vascular cells, yielding protective effects, regardless of gender. Such actions are mediated by ER (ER-alpha (ERα), ER-beta (ERß), or G protein-coupled ER (GPER)) through genomic or non-genomic pathways, which regulate cardiovascular function and prevent tissue remodeling. Despite the extensive knowledge on the cardioprotective effects of estrogen, clinical studies conducted on myocardial infarction (MI) and cardiovascular diseases still include favorable and unfavorable profiles. The purpose of this review is to provide up-to-date information regarding molecular, preclinical, and clinical aspects of cardiovascular E2 effects and ER modulation as a potential therapeutic target for the treatment of MI-induced cardiac dysfunction.

The Genetic Variants -717T>C (rs2794521), 1444G>A (rs1130864), and 1846 C > T (rs1205) of CRP Gene, Their Haplotypes, and Their Association with Serum CRP Levels, Acute Coronary Syndrome, and Diabetes in Patients from Western Mexico.

Background: C-reactive protein (CRP) is involved in inflammatory pathways that are associated with the onset and progression of type 2 diabetes mellitus (T2DM) as well as an increased risk of an acute coronary syndrome (ACS). This research aimed to evaluate the potential association of the genetic variants -717T>C, 1444G>A, and 1846 C > T of CRP gene on CRP levels, ACS, and T2DM in participants from Western Mexico. Methods: Six hundred three participants were studied: (1) control group (CG); (2) ACS participants classified as unstable angina (UA), myocardial infarction without ST-segment elevation (NSTEMI), and myocardial infarction with ST-segment elevation (STEMI); (3) T2DM Participants; and (4) ACS plus T2DM participants (ACS+T2DM). Genetic variants were genotyped using allelic discrimination with TaqMan® probes, and high-sensitivity CRP (hs-CRP) was measured by Turbidimetry. Results: TAC haplotype frequency was significantly higher in ACS+T2DM versus CG and versus ACS participants (odds ratio [OR] = 2.774, P = 0.017 and OR = 3.479, P = 0.020, respectively). hs-CRP levels were especially higher for ACS and for ACS+T2DM participants with respect to CG and T2DM (with P < 0.0001). We observed higher hs-CRP levels in NSTEMI and STEMI versus UA in ACS scenario (P = 0.001, P = 0.027, respectively) and for ACS+T2DM scenario (P = 0.0001, P = 0.002, respectively). Conclusion: hs-CRP level fluctuations are related to the presence of T2DM and the presence and severity of ACS. Very high levels (>10 mg/L) are a risk marker of cardiovascular complications. Our results demonstrate a possible relationship between TAC haplotype and an increased risk for T2DM and ACS.

Association of the PSRC1 rs599839 Variant with Coronary Artery Disease in a Mexican Population.

Background and Objectives: Coronary artery disease (CAD) is a major health problem in México. The identification of modifiable risk factors and genetic biomarkers is crucial for an integrative and personalized CAD risk evaluation. In this work, we aimed to validate in a Mexican population a set of eight selected polymorphisms previously associated with CAD, myocardial infarction (MI), or dyslipidemia. Materials and Methods: A sample of 907 subjects (394 CAD cases and 513 controls) 40-80 years old was genotyped for eight loci: PSRC1 (rs599839), MRAS (rs9818870), BTN2A1 (rs6929846), MTHFD1L (rs6922269), CDKN2B (rs1333049), KIAA1462 (rs3739998), CXCL12 (rs501120), and HNF1A (rs2259816). The association between single nucleotide polymorphisms (SNPs) and CAD was evaluated by logistic regression models. Results: Multiple logistic regression analysis with adjustment by age, gender, and body mass index showed that rs599839 was significantly associated with CAD (ORADD = 0.72, p = 0.009; ORDOM = 0.66, p = 0.007). Conclusions: The PSRC1 rs599839 polymorphism shows a significant protective association with CAD in this sample of the Mexican population.

The rs46522 Polymorphism of the Ubiquitin-Conjugating Enzyme E2Z Gene Is Associated with Abnormal Metabolic Parameters in Patients with Myocardial Infarction: The Genetics of Atherosclerosis Disease Mexican Study.

The participation of ubiquitin-conjugating enzyme E2Z (UBE2Z) in atherosclerosis has been reported. We aimed to evaluate the association of the rs46522 polymorphism of the UBE2Z gene with myocardial infarction (MI) and other clinical and metabolic components in the Mexican population. A total of 2128 individuals (1023 patients with MI and 1105 healthy controls) were included. rs46522 was genotyped using the 5' exonuclease TaqMan genotyping assay. A similar polymorphism distribution was observed between patients and healthy controls. The association between rs46522 polymorphism and cardiometabolic parameters was evaluated separately in the two groups. In the control group, rs46522 polymorphism was associated with increased risk of developing low-density lipoprotein cholesterol ≥130 mg/dL (odds ratio [OR] = 1.249, padditive = 0.018; OR = 1.479, precessive = 0.015; OR = 1.589, pcodominant 2 = 0.013). On the other hand, in MI patients, it was observed that rs46522 polymorphism was associated with an increased risk of developing high levels of alanine transaminase (OR = 1.297, pheterozygote = 0.043) and aspartate transaminase (OR = 1.453, pdominant = 0.009; OR = 1.592, pheterozygote = 0.001; OR = 1.632, pcodominant 1 = 0.001). Our results suggest that the UBE2Z gene rs46522 polymorphism is associated with abnormal metabolic parameters in Mexican patients with MI.

Quantification of DNA Damage in Different Tissues in Rats with Heart Failure.

BACKGROUND: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. OBJECTIVE: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. METHODS: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. RESULTS: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). CONCLUSION: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.

THE BRANCHED-CHAIN AMINO ACID TRANSAMINASE 1 -23C/G POLYMORPHISM CONFERS PROTECTION AGAINST ACUTE CORONARY SYNDROME.

BACKGROUND: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). OBJECTIVE: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. METHODS: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5' TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. RESULTS: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. CONCLUSION: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.

Quantification of DNA Damage in Different Tissues in Rats with Heart Failure / Quantificação de Dano em DNA em Diferentes Tecidos em Ratos com Insuficiência Cardíaca

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.

Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.

The branched-chain amino acid transaminase 1 -23c/g polymorphism confers protection against acute coronary syndrome

ABSTRACT Background: Previous studies have shown an association between polymorphisms of the BAT1-NF-κB inhibitor-like-1 (NFKBIL1)-LTA genomic region and susceptibility to myocardial infarction and acute coronary syndrome (ACS). Objective: The objective of the study was to study the role of three polymorphisms in the BAT1, NFKBIL1, and LTA genes on the susceptibility or protection against ACS; we included a group of cases-controls from Central Mexico. Methods: The BAT1 rs2239527C/G, NFKBIL1 rs2071592T/A, and LTA rs1800683G/A polymorphisms were genotyped using a 5' TaqMan assay in a group of 625 patients with ACS and 617 healthy controls. Results: Under a recessive model, the BAT1 -23C/G (rs2239527) polymorphism showed an association with protection against ACS (odds ratio = 0.56, and p-corrected = 0.019). In contrast, the genotype and allele frequencies of the NFKBIL1 rs2071592T/A and LTA rs1800683G/A polymorphisms were similar between ACS patients and controls and no association was identified. Conclusion: Our data suggest an association between the BAT1 -23C/G polymorphism and protection against ACS in Mexican patients.

Clinical significance and correlation of microRNA-21 expression and the neutrophil-lymphocyte ratio in patients with acute myocardial infarction.

OBJECTIVES: To explore the clinical significance and correlation of microRNA-21 (miR-21) and the neutrophil-lymphocyte ratio (NLR) in patients with acute myocardial infarction (AMI). METHODS: The observation group contained 184 patients, while the control group contained 150 patients. The expression of miR-21 in the serum of each group was detected by qRT-PCR. RESULTS: A total of 184 patients and their family members were followed-up for 30 days, among which 35 patients died and 149 patients survived, resulting in a survival rate of 80.97%. According to univariate analysis, there were significant differences in age, cardiac troponin (cTn), heart rate, Killip grade, percutaneous coronary intervention (PCI) operation rate, miR-21 and NLR. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) values of miR-21 and NLR for the diagnosis of AMI were 0.909 and 0.868, respectively, and the area under the combined detection curve was 0.960. In the Kaplan-Meier survival analysis, the survival of patients with high miR-21 expression and NLR was significantly higher than that of patients with low miR-21 expression and NLR (p=0.027; p=0.001). The correlation showed that miR-21 expression in serum was positively correlated with the NLR in the observation group (r=0.528, p<0.05). cTn, heart rate, Killip classification, PCI operation rate, miR-21, NLR are independent risk factors for AMI. CONCLUSION: miR-21 and NLR play a role in the diagnosis of AMI and can be used as predictors for the survival of AMI.

HDL-Targeted Therapies During Myocardial Infarction.

It is now apparent that a variety of deleterious mechanisms intrinsic to myocardial infarction (MI) exists and underlies its high residual lethality. Indeed, despite effective coronary patency therapies, ischemia and reperfusion (I/R) injury accounts for about 50% of the infarcted mass. In this context, recent studies in animal models have demonstrated that coronary reperfusion with high-density lipoproteins (HDL) may reduce MI size in up to 30%. A spectrum of mechanisms mediated by either HDL-related apolipoproteins or phospholipids attenuates myocardial cell death. Hence, promising therapeutic approaches such as infusion of reconstituted HDL particles, new HDL by genomic therapy, or the infusion of apoA-I mimetic peptides have been sought as a way of ensuring protection against I/R injury. In this review, we will explore the limitations and potential therapeutic effects of HDL therapies during the acute phase of MI.