title: Functional and structural impact of pirfenidone on the alterations of cardiac disease and diabetes mellitus.
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.
authors.affiliation: Department of Biochemistry, Cinvestav-IPN, AP 14-740, México City, DF 07000, Mexico. Electronic address: gavila@cinvestav.mx.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Avila
authors.affiliation: Department of Biochemistry, Cinvestav-IPN, AP 14-740, México City, DF 07000, Mexico.
authors.forename: Diana Stephanie
authors.initials: DS
authors.lastname: Osornio-Garduño
authors.affiliation: Department of Biochemistry, Cinvestav-IPN, AP 14-740, México City, DF 07000, Mexico.
authors.forename: Erick Benjamín
authors.initials: EB
authors.lastname: Ríos-Pérez
authors.affiliation: Department of Biochemistry, Cinvestav-IPN, AP 14-740, México City, DF 07000, Mexico.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ramos-Mondragón
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D011728:Pyridones; D053773:Transforming Growth Factor beta1; C093844:pirfenidone; D002118:Calcium
keywords: Action potential; Calcium channel; Cardiac myocyte; Intracellular calcium; Ion channel; TGF-β1