RESUMO
BACKGROUND: Mitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure. METHODS: Myocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real-time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion-fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry. RESULTS: The following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT-ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM. CONCLUSIONS: Heart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion-fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.
RESUMO
AIM: Obesity is a well-known risk factor in the cardiovascular disease continuum. However, its clinical effects are multimodal, perplexed and non-unanimously understood. Our aim was to assess the prevalence and effects of obesity on the cardiometabolic risk factors and systolic function of left ventricle ejection fraction (LVEF) in patients scheduled for cardiovascular rehabilitation. METHODS: A cohort of 302 consecutive patients recently treated for ischaemic or valvular heart disease was matched according to the existence of obesity, defined with body mass index (BMI ≥ 30 kg/m(2) ; n = 90 vs. 212), and the advanced grade of obesity (BMI ≥ 35 kg/m(2) ; n = 19 vs. 283). Nutritional risk screening was performed using the standardised NRS-2002 tool. RESULTS: The mean age of patients was 62.4 ± 11.2 (range 23-86) years; there were more men than women 244 (80.8%) : 58 (19.2%). Group of obese conveyed higher prevalence of ischaemic heart disease than non-obese (OR = 2.69; 95% CI: 1.01-7.20; p = 0.048); while the difference was insignificant for the advanced grade of obesity (n = 17; 89.5%) vs. controls (n = 233; 82.3%; p > 0.05). There was no significant difference in prevalence of other comorbidities (diabetes, glucose intolerance, hypercholesterolaemia, chronic renal and chronic obstructive pulmonary disease) between studied groups (p > 0.05). Utilisation of lipid-lowering drugs was of similar range between the studied groups (p > 0.05), respectively. LVEF (%) was 50.5 ± 8.2 vs. 50.7 ± 7.7 (p > 0.05) and 50.6 ± 7.8 vs. 49.6 ± 10.9 (p > 0.05; Rho = 0.001; p > 0.05), respectively. CONCLUSION: In studied set of patients, BMI positively correlated with left ventricle dimension and thickness. No significant connection of obesity was found with the prevalence of chronic comorbidities, increased nutritional risk, laboratory diagnostics or systolic function of left ventricle. Existence of obesity paradox in clinical practice was in part reaffirmed with our study.