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Functional and structural impact of pirfenidone on the alterations of cardiac disease and diabetes mellitus.

Published on Nov 1, 2014in Cell Calcium3.932
· DOI :10.1016/j.ceca.2014.07.008
Guillermo Avila17
Estimated H-index: 17
(CINVESTAV),
Diana Stephanie Osornio-Garduño2
Estimated H-index: 2
(CINVESTAV)
+ 1 AuthorsRoberto Ramos-Mondragón6
Estimated H-index: 6
(CINVESTAV)
Abstract
Abstract A synthetic compound, termed pirfenidone (PFD), is considered promising for the treatment of cardiac disease. It leads to beneficial effects in animal models of diabetes mellitus (DM); as well as in heart attack, atrial fibrillation, muscular dystrophy, and diabetic cardiomyopathy (DC). The latter is a result of alterations linked to metabolic syndrome as they promote cardiac hypertrophy, fibrosis and contractile dysfunction. Although reduced level of fibrosis and stiffness represent an essential step in the mechanism of PFD action, a wide range of functional effects might also contribute to the therapeutic benefits. For example, PFD stimulates L-type voltage-gated Ca 2+ channels (LTCCs), which are pivotal for a process known as excitation–contraction coupling (ECC). Recent evidence suggests that these two types of actions – namely structural and functional – aid in treating both cardiac disease and DM. This view is supported by the fact that in DC, for example, systolic dysfunction arises from both cardiac stiffness linked to fibrosis and down-regulation of ECC. Thus, not surprisingly, clinical trials have been conducted with PFD in the settings of DM, for treating not only cardiac but also renal disease. This review presents all these concepts, along with the possible mechanisms and pathophysiological consequences.
  • References (96)
  • Citations (7)
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References96
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#2Lucman A. Anwer (Alfaisal University)H-Index: 2
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Transforming growth factor-β1 (TGF-β1) is related to the degree of atrial fibrosis and plays critical roles in the induction and perpetuation of atrial fibrillation (AF). To investigate the association of the common promoter polymorphism rs1800469 in the TGF-β1 gene (TGFB1) with the risk of AF in Chinese Han population, we carried out a case-control study of two hospital-based independent populations: Southeast Chinese population (581 patients with AF and 723 controls), and Northeast Chinese pop...
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Aims On the basis of its ability to inhibit fibrosis, pirfenidone has drawn the attention as an intriguing candidate for treating cardiac disease. However, its precise electrophysiological effects have yet to be elucidated. Here, we have investigated its potential to modulate ion channels. Methods and results Adult rat cardiac myocytes were investigated using whole-cell patch-clamp, western-blot and qRT-PCR techniques. Pirfenidone increased the density of L-type Ca2+ current ( I CaL, 50–100%), w...
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