La ivabradina induce cardioprotección previniendo la degradación de la matriz extracelular inducida por shock cardiogénico

Tesoro, Laura; Ramírez-Carracedo, Rafael; Hernández, Ignacio; Díez-Mata, Javier; Pascual, Marina; Saura, Marta; Sanmartín, Marcelo; Zamorano, José Luís; Zaragoza, Carlos

doi:10.1016/j.recesp.2020.09.018

Cited by 2 publications

(1 citation statement)

References 32 publications

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“…The complex CyPA/EMMPRIN worsens myocardial damage by contributing to leukocyte re-cruitment [4,25] and also by inducing extracellular matrix degradation through EMMPRINinduced matrix metalloproteinase activation [26]. Recently, we found that Ivabradine induces cardiac protection by inhibiting EMMPRIN-mediated MMP activation [8,27], but the specific role of the complex CyPA/EMMPRIN has not been previously investigated.…”

Section: Discussionmentioning

confidence: 99%

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

Hernández

Tesoro

Ramírez-Carracedo

et al. 2021

IJMS

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In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.

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Section: Discussionmentioning

confidence: 99%

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

Hernández

Tesoro

Ramírez-Carracedo

et al. 2021

IJMS

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Therapeutic Use and Molecular Aspects of Ivabradine in Cardiac Remodeling: A Review

Kamisah

Hassan

2023

IJMS

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Cardiac remodeling can cause ventricular dysfunction and progress to heart failure, a cardiovascular disease that claims many lives globally. Ivabradine, a funny channel (If) inhibitor, is used in patients with chronic heart failure as an adjunct to other heart failure medications. This review aims to gather updated information regarding the therapeutic use and mechanism of action of ivabradine in heart failure. The drug reduces elevated resting heart rate, which is linked to increased morbidity and mortality in patients with heart failure. Its use is associated with improved cardiac function, structure, and quality of life in the patients. Ivabradine exerts several pleiotropic effects, including an antiremodeling property, which are independent of its principal heart-rate-reducing effects. Its suppressive effects on cardiac remodeling have been demonstrated in animal models of cardiac remodeling and heart failure. It reduces myocardial fibrosis, apoptosis, inflammation, and oxidative stress as well as increases autophagy in the animals. It also modulates myocardial calcium homeostasis, neurohumoral systems, and energy metabolism. However, its role in improving heart failure remains unclear. Therefore, elucidating its molecular mechanisms is imperative and would aid in the design of future studies.

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La ivabradina induce cardioprotección previniendo la degradación de la matriz extracelular inducida por shock cardiogénico

Cited by 2 publications

References 32 publications

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

Therapeutic Use and Molecular Aspects of Ivabradine in Cardiac Remodeling: A Review

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