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Objectives : Many studies indicate the involvement of transient receptor potential (TRP) channels in the development of heart hypertrophy. However, the data is often conflicted and has originated in animal models. Here, we provide systematic analysis of TRP channels expression in human failing myocardium. Methods and results : Left-ventricular tissue samples were isolated from explanted hearts of NYHA III-IV patients undergoing heart transplants (n = 43). Quantitative real-time PCR was performed to assess the mRNA levels of TRPC, TRPM and TRPV channels. Analysis of functional, clinical and biochemical data was used to confirm an end-stage heart failure diagnosis. Compared to myocardium samples from healthy donor hearts (n = 5), we detected a distinct increase in the expression of TRPC1, TRPC5, TRPM4 and TRPM7, and decreased expression of TRPC4 and TRPV2. These changes were not dependent on gender, clinical or biochemical parameters, nor functional parameters of the heart. We detected, however, a significant correlation of TRPC1 and MEF2c expression. Conclusions : The end-stage heart failure displays distinct expressional changes of TRP channels. Our findings provide a systematic description of TRP channel expression in human heart failure. The results highlight the complex interplay between TRP channels and the need for deeper analysis of early stages of hypertrophy and heart failure development.

Background: Cardiac troponin I (cTnI) is a valuable prognostic biomarker in patients with chronic heart failure (CHF). However, the prognostic importance of cTnI in patients who received cardiac resynchronisation therapy (CRT) remains unknown. The aim of this prospective study was to determine the prognostic value of high-sensitive cTnI (hs-cTnI) in CHF patients receiving CRT., Methods: We performed measurements of baseline hs-cTnI levels in CRT patients with ischaemic as well as nonischaemic aetiology of CHF, and we investigated their possible association with response to CRT and survival of patients., Results: Ninety consecutive CRT patients (mean age 64 ± 9 years, 71 men) were included. According to the best cut-off value of hs-cTnI level to predict CRT response and all cause mortality, patients were divided into group 1 (hs-cTnI level ≥6.5 ng/l, n = 46) and group 2 (hs-cTnI level <6.5 ng/l, n = 44). During the follow-up period (1155 ± 406 days), 47% of patients were CRT responders (30% in group 1 and 64% in group 2, p = .002) and 31% of patients died from any cause (48% in group 1 and 14% in group 2, p = .001). Regression analysis showed that hs-cTnI level <6.5 ng/l was an independent predictor of CRT response (OR 3.49, p = .019) and that hs-cTnI level ≥6.5 ng/l was an independent predictor of all cause mortality (HR 3.01, p = .021)., Conclusion: The hs-cTnI can be an useful biomarker with prognostic value in patients receiving CRT.

Background: Cell loss and subsequent deterioration of contractile function are hallmarks of chronic heart failure (HF). While apoptosis has been investigated as a participant in the progression of HF, it is unlikely that it accounts for the total amount of non-functional tissue. In addition, there is evidence for the presence of necrotic cardiomyocytes in HF. Therefore, the objective of this study was to investigate the necroptotic proteins regulating necroptosis, a form of programmed necrosis, and thereby assess its potential role in human end-stage HF., Methods: Left ventricular samples of healthy controls (C) and patients with end-stage HF due to myocardial infarction (CAD) or dilated cardiomyopathy (DCM) were studied. Immunoblotting for necroptotic and apoptotic markers was performed. Triton X-114 fractionated samples were analyzed to study differences in subcellular localization., Results: Elevated expression of RIP1 (receptor-interacting protein), pSer 227 -RIP3 and its total levels were observed in HF groups compared to controls. On the other hand, caspase-8 expression, a proapoptotic protease negatively regulating necroptosis, was downregulated suggesting activation of necroptosis signaling. Total mixed-lineage kinase domain-like protein (MLKL) expression did not differ among the groups; however, active cytotoxic forms of MLKL were present in all HF samples while they were expressed at almost undetectable levels in controls. Interestingly, pThr 357 -MLKL unlike pSer 358 -MLKL, was higher in DCM than CAD. In HF, the subcellular localization of both RIP3 and pThr 357 -MLKL was consistent with activation of necroptosis signaling. Expression of main apoptotic markers has not indicated importance of apoptosis., Conclusions: This is the first evidence showing that human HF of CAD or DCM etiology is positive for markers of necroptosis which may be involved in the development of HF.

Heart remodeling occurs as a compensation mechanism for the massive loss of tissue during initial heart failure and the consequent inflammation process. During heart remodeling fibroblasts differentiate to myofibroblasts activate their secretion functions and produce elevated amounts, of extracellular matrix (ECM) proteins, mostly collagen, that form scar tissue and alter the normal degradation of ECM. Scar formation does replace the damaged tissue structurally; however, it impedes the normal contractive function of cardiomyocytes (CMs) and results in longlasting effects after heart failure. Besides CMs and cardiac fibroblasts, endothelial cells (ECs) and circulating endothelial progenitor cells (cEPCs) contribute to heart repair. This review summarizes the current knowledge of EC-CM crosstalk in cardiac fibrosis (CF), the role of cEPCs in heart regeneration and the contribution of Endothelial-mesenchymal transition (EndoMT). [ABSTRACT FROM AUTHOR]