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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 Calcium3.93
· DOI :10.1016/j.ceca.2014.07.008
Guillermo Avila16
Estimated H-index: 16
(CINVESTAV),
Diana Stephanie Osornio-Garduño2
Estimated H-index: 2
(CINVESTAV)
+ 1 AuthorsRoberto Ramos-Mondragón6
Estimated H-index: 6
(CINVESTAV)
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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 (94)
  • Citations (7)
Cite
References94
Newest
Published on Feb 1, 2014in European Journal of Pharmacology3.17
Mohammad Abrar Shareef3
Estimated H-index: 3
(Alfaisal University),
Lucman A. Anwer2
Estimated H-index: 2
(Alfaisal University),
Coralie Poizat18
Estimated H-index: 18
(SDSU: San Diego State University)
Abstract Calcium (Ca 2+ ) recycling is key for effective relaxation of the cardiac muscle. Failure to properly recycle calcium through the sarcoplasmic reticulum (SR) results in severe impairment of myocardial relaxation and consequently alteration of the “beat-to-beat” heart rhythm and contractile function. The Sarco(Endo)plasmic reticulum Ca 2+ ATPase (SERCA) is instrumental for recycling cytosolic Ca 2+ into the lumen of the SR. Among the many SERCA isoforms identified so far, SERCA2a is rest...
Published on Dec 12, 2013in PLOS ONE2.78
Weixing Zheng5
Estimated H-index: 5
(Fujian Medical University),
Chenghui Yan4
Estimated H-index: 4
(Shenyang)
+ 7 AuthorsMingfang Huang6
Estimated H-index: 6
(Fujian Medical University)
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...
Published on Dec 1, 2013in BMC Cardiovascular Disorders1.95
Ines Nevelsteen8
Estimated H-index: 8
(Katholieke Universiteit Leuven),
Virginie Bito21
Estimated H-index: 21
(Katholieke Universiteit Leuven)
+ 5 AuthorsPaul Herijgers38
Estimated H-index: 38
(Katholieke Universiteit Leuven)
Background Diabetic cardiomyopathy is characterized by systolic and early diastolic ventricular dysfunction. In the metabolic syndrome (MS), ventricular stiffness is additionally increased in a later stage. It is unknown whether this is related to intrinsic cardiomyocyte dysfunction, extrinsic factors influencing cardiomyocyte contractility and/or cardiac function, or a combination of both. A first aim was to study cardiomyocyte contractility and Ca2+ handling in vitro in a mouse model of MS. A ...
Jaime Balderas-Villalobos2
Estimated H-index: 2
(IPN: Instituto Politécnico Nacional),
Tzindilu Molina-Muñoz2
Estimated H-index: 2
(IPN: Instituto Politécnico Nacional)
+ 3 AuthorsNorma L. Gómez-Viquez3
Estimated H-index: 3
(IPN: Instituto Politécnico Nacional)
Ca+ mishandling due to impaired activity of cardiac sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) has been associated with the development of left ventricular diastolic dysfunction in insulin-resistant cardiomyopathy. However, the molecular causes underlying SERCA2a alterations induced by insulin resistance and related metabolic disorders, such as metabolic syndrome (MetS), are not completely understood. In this study, we used a sucrose-fed rat model of MetS to test the hypothesis that decr...
Published on Jun 1, 2013in Cardiovascular Toxicology2.63
Ayca Bilginoglu8
Estimated H-index: 8
,
Hilmi Burak Kandilci4
Estimated H-index: 4
(Ankara University),
Belma Turan27
Estimated H-index: 27
(Ankara University)
Intracellular Na+ ([Na+] i ) is an important modulator of excitation–contraction coupling via regulating Ca2+ efflux/influx, and no investigation has been so far performed in diabetic rat heart. Here, we examined whether any change of [Na+] i in paced cardiomyocytes could contribute to functional alterations during diabetes. Slowing down in depolarization phase of the action potential, small but significant decrease in its amplitude with a slight depolarized resting membrane potential was traced...
Published on Jan 1, 2013in Future Cardiology
Jordi Heijman17
Estimated H-index: 17
,
Niels Voigt33
Estimated H-index: 33
,
Dobromir Dobrev67
Estimated H-index: 67
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and has a significant impact on morbidity and mortality. Current antiarrhythmic drugs for AF suffer from limited safety and efficacy, probably because they were not designed based on specific pathological mechanisms. Recent research has provided important insights into the mechanisms contributing to AF and highlighted several potential novel antiarrhythmic strategies. In this review, we highlight the main pathological mechanisms o...
Published on Jan 1, 2013in The Cardiology1.56
Yongliang Wang1
Estimated H-index: 1
,
Yongquan Wu2
Estimated H-index: 2
+ 2 AuthorsHongwei Li1
Estimated H-index: 1
Objectives: Left ventricular remodeling is a frequent complication of hypertension with no therapeutic treatment available for the subsequent onset of myocardial
Published on Jan 1, 2013in Expert Opinion on Pharmacotherapy3.04
Harpreet Lota4
Estimated H-index: 4
,
Athol U. Wells81
Estimated H-index: 81
(National Health Service)
Introduction: Novel compounds targeting various aspects of fibrogenesis have been developed consequent to the increasing knowledge of the pathogenetic mechanisms of the interstitial lung diseases (ILDs). The authors review the evolution of treatment approaches in the ILDs, informed by recent placebo-controlled trials, and discuss current clinical trials in which emerging pathogenetic mechanisms are targeted as novel therapeutic agents. Areas covered: In idiopathic pulmonary fibrosis (IPF), recen...
Published on Nov 1, 2012in Cardiovascular Research7.01
Roberto Ramos-Mondragón6
Estimated H-index: 6
(CINVESTAV),
Carlos A. Galindo2
Estimated H-index: 2
(CINVESTAV)
+ 4 AuthorsGuillermo Avila16
Estimated H-index: 16
(CINVESTAV)
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...
Published on Oct 24, 2012in Current Cardiology Reviews
Omar Asghar15
Estimated H-index: 15
,
Uazman Alam18
Estimated H-index: 18
+ 3 AuthorsRayaz A. Malik51
Estimated H-index: 51
The last few decades have witnessed a global rise in adult obesity of epidemic proportions. The potential impact of this is emphasized when one considers that body mass index (BMI) is a powerful predictor of death, type 2 diabetes (T2DM) and cardiovascular (CV) morbidity and mortality [1, 2]. Similarly we have witnessed a parallel rise in the incidence of atrial fibrillation (AF), the commonest sustained cardiac arrhythmia, which is also a significant cause of cardiovascular morbidity and mortal...
Cited By7
Newest
Published on Jan 5, 2019in Current Medical Research and Opinion2.35
Andrea Vianello22
Estimated H-index: 22
(UNIPD: University of Padua),
Beatrice Molena8
Estimated H-index: 8
(UNIPD: University of Padua)
+ 5 AuthorsMarina Saetta64
Estimated H-index: 64
(UNIPD: University of Padua)
AbstractObjective: To examine the effect of pirfenidone on the survival of patients hospitalized due to acute exacerbation of idiopathic pulmonary fibrosis (AE–IPF).Methods: The outcomes of 11 consecutive AE–IPF patients who were receiving pirfenidone treatment when they were admitted to a respiratory intensive care unit (RICU) for acute respiratory failure (ARF) (treatment group) were retrospectively compared with those of 9 patients who were not on pirfenidone treatment at admission (control g...
Published on Dec 13, 2018in Frontiers in Physiology3.20
Adrián Monsalvo-Villegas1
Estimated H-index: 1
(CINVESTAV),
Diana Stephanie Osornio-Garduño2
Estimated H-index: 2
(CINVESTAV),
Guillermo Avila16
Estimated H-index: 16
(CINVESTAV)
Pirfenidone (PFD) is used to treat human pulmonary fibrosis. Its administration to animals with distinct forms of cardiovascular disease results in striking improvement in cardiac performance. Here, its functional impact on cardiac myocytes was investigated. Cells were kept 1-2 d under either control culture conditions or the presence of PFD (1 mM). Subsequently, they were subjected to electrical stimulation to assess the levels of contractility and intracellular Ca2+. The PFD treatment promoted...
Published on Mar 27, 2018in Frontiers in Physiology3.20
Anandharajan Rathinasabapathy6
Estimated H-index: 6
(UF: University of Florida),
Alana Horowitz3
Estimated H-index: 3
(UF: University of Florida)
+ 11 AuthorsMohan K. Raizada59
Estimated H-index: 59
(UF: University of Florida)
Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH) is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimul...
Published on Nov 1, 2017in Diabetes Research and Clinical Practice3.24
Yiyang Yue1
Estimated H-index: 1
(ZJU: Zhejiang University),
Ke Meng1
Estimated H-index: 1
(ZJU: Zhejiang University)
+ 1 AuthorsXiaoming Zhang1
Estimated H-index: 1
(ZJU: Zhejiang University)
Abstract Cardiovascular diseases account for the major cause of morbidity and mortality among individuals with diabetes. The diabetic cardiomyopathy (DCM) is a type of diabetic cardiovascular disease, which further directs to the heart failure. The researchers found that diabetes induced cardiac fibrosis plays a vital role in several of the pathological changes that associated with DCM, causing left ventricular hypertrophy (LVH), diastolic dysfunction and systolic dysfunction. However, the mecha...
Published on Feb 1, 2017in Scientific Reports4.01
Chunmei Li15
Estimated H-index: 15
,
Rui Han1
Estimated H-index: 1
+ 5 AuthorsJingwei Tian19
Estimated H-index: 19
Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis
Published on Jan 1, 2016in Intractable & Rare Diseases Research
Abhinav Agrawal6
Estimated H-index: 6
(Monmouth Medical Center),
Isha Verma3
Estimated H-index: 3
(Monmouth Medical Center)
+ 2 AuthorsRutuja R Sikachi3
Estimated H-index: 3
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, parenchymal disease of the lung with an estimated prevalence of 14–43 per 100,000. Patient usually presents with coughing and exertional dyspnea, which can lead to acute respiratory failure. IPF has been associated with various co-morbidities such as lung cancer, emphysema, obstructive sleep apnea (OSA), GERD and multiple cardiovascular consequences. The cardiovascular manifestations of IPF include pulmonary hypertension, heart failu...
Published on Jul 9, 2015
Anna Wysocka2
Estimated H-index: 2
,
Marta Karaś-Głodek , Andrzej Wysokiński8
Estimated H-index: 8
Summary Atrial fibrillation is the most frequent arrhythmia, that still remains one of the most diffficult to pharmacological management. Antiarrhythmic drugs have been widely used to restore sinus rhythm and to prevent reccurence of arrhythmia, but pharmacological therapy is limited to several available agents, because of insufficient efficiacy and the significant risk of serious adverse effects. In patients with atrial fibrillation without structural heart disease, it is possible to perform ph...
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