Development of Mild Aortic Valve Stenosis in a Rabbit Model of Hypertension

Cuniberti, Luis; Stutzbach, Pablo; Guevara, Eduardo; Yannarelli, Gustavo; Laguens, Rubén P.; Favaloro, Roberto

doi:10.1016/j.jacc.2005.12.070

Cited by 32 publications

(20 citation statements)

References 32 publications

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“…Echocardiography has been successfully used in various rabbit models to study LV remodeling and cardiac function [22,23]. In the present study, IVA significantly improved LV MPI, which is a simple and non-geometric index that takes into account systolic and diastolic functions independently of HR.…”

Section: Discussionmentioning

confidence: 56%

Heart Rate Reduction by Ivabradine Reduces Diastolic Dysfunction and Cardiac Fibrosis

et al. 2010

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Objectives: To determine if heart rate (HR) reduction with ivabradine (IVA), a selective inhibitor of the pacemaker I_f current, prevents cardiac dysfunction associated with dyslipidemia. Methods: New Zealand White rabbits received either a standard diet, a 0.5% cholesterol-enriched diet only (CD), or a 0.5% CD with IVA (17 mg/kg/day) for 12 weeks. HR, left ventricular (LV) systolic function, diastolic function and LV regional myocardial performance index (MPI) were studied using echocardiography. Histological analysis included cardiac interstitial fibrosis and collagen type I fibers. Plasma levels of angiotensin II and aldosterone were quantified by immunoassays. Results: IVA reduced HR by approximately 11%. IVA improved MPI and attenuated LV diastolic dysfunction (DD) (92% mild and 8% moderate DD with IVA vs. 54% mild and 46% moderate DD in CD group). IVA also reduced atrial fibrosis (p = 0.027), ventricular fibrosis (p = 0.0002) and ventricular collagen type I (p = 0.0042). IVA decreased plasma angiotensin II levels (p = 0.042), and both angiotensin II and aldosterone levels were correlated with HR (p = 0.038 and 0.008). Conclusion: Selective HR reduction with IVA reduces DD and cardiac fibrosis in hypercholesterolemic rabbits. These beneficial effects of IVA support testing pure HR reduction in patients with diastolic heart failure.

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Section: Discussionmentioning

confidence: 56%

Heart Rate Reduction by Ivabradine Reduces Diastolic Dysfunction and Cardiac Fibrosis

et al. 2010

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“…However, drugs targeting these pathways have had limited success, which has been attributed to their failure to address the concurrent mechanical signals that play a crucial role in the initiation and progression of disease (Frangogiannis, 2014). Conditions that favor increased local tissue strains and stresses increase the risk of developing fibrotic disease in affected structures by altering the behavior and phenotype of cardiac cells, which contributes to maladaptive tissue remodeling (Cuniberti et al, 2006;Merryman et al, 2006). Therefore, determining how various cardiac cells respond to changing mechanical environments will aid our understanding of the development of heart disease and potentially uncover new targets for future therapy (Fig.…”

Section: Introductionmentioning

confidence: 99%

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Schroer

Merryman

2015

Journal of Cell Science

117

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Fibrotic cardiac disease, a leading cause of death worldwide, manifests as substantial loss of function following maladaptive tissue remodeling. Fibrosis can affect both the heart valves and the myocardium and is characterized by the activation of fibroblasts and accumulation of extracellular matrix. Valvular interstitial cells and cardiac fibroblasts, the cell types responsible for maintenance of cardiac extracellular matrix, are sensitive to changing mechanical environments, and their ability to sense and respond to mechanical forces determines both normal development and the progression of disease. Recent studies have uncovered specific adhesion proteins and mechano-sensitive signaling pathways that contribute to the progression of fibrosis. Integrins form adhesions with the extracellular matrix, and respond to changes in substrate stiffness and extracellular matrix composition. Cadherins mechanically link neighboring cells and are likely to contribute to fibrotic disease propagation. Finally, transition to the active myofibroblast phenotype leads to maladaptive tissue remodeling and enhanced mechanotransductive signaling, forming a positive feedback loop that contributes to heart failure. This Commentary summarizes recent findings on the role of mechanotransduction through integrins and cadherins to perpetuate mechanically induced differentiation and fibrosis in the context of cardiac disease.

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“…It proves that concomitant hypertension in AS is significant for prognosis. However, Cuniberli et al reported the hypothesis of a causal link between hypertension and AS [12]. In this context hypertension in AS population should be assessed in these entities, prognostic and causative.…”

Section: Discussionmentioning

confidence: 99%