Preclinical rodent models of cardiac fibrosis

Abstract

Cardiac fibrosis (scarring), characterised by an increased deposition of extracellular matrix (ECM) proteins, is a hallmark of most types of cardiovascular disease and plays an essential role in heart failure progression. Inhibition of cardiac fibrosis could improve outcomes in patients with cardiovascular diseases and particularly heart failure. However, pharmacological treatment of the ECM build‐up is still lacking. In this context, preclinical models of heart disease are important tools for understanding the complex pathogenesis involved in the development of cardiac fibrosis which in turn could identify new therapeutic targets and the facilitation of antifibrotic drug discovery. Many preclinical models have been used to study cardiac fibrosis and each model provides mechanistic insights into the many factors that contribute to cardiac fibrosis. This review discusses the most frequently used rodent models of cardiac fibrosis and also provides context for the use of particular models of heart failure. LINKED ARTICLES This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc

Myocardial Interstitial Fibrosis in Hypertensive Heart Disease: From Mechanisms to Clinical Management

“…A large number of experimental studies have shown that in animal models of systemic hypertension (eg, spontaneous genetic hypertension, renovascular, exogenous induction, and transgenic models) adverse LV remodeling and MIF begin after elevation in BP and both progress in parallel thereafter (Figure 2). 36,37 Mechanical stress that occurs due to hypertension-induced LV pressure overload can be sensed by resident cardiac fibroblasts by cell surface receptors (eg, integrins and discoidin domain receptors) 38 that mediate mechanotransduction signaling involved in fibroblast activation, as well as differentiation into myofibroblasts. Moreover, the extracellular matrix functions as a reservoir of profibrotic signaling molecules that can be released upon mechanical stress.…”

The Angiotensin AT2Receptor: From a Binding Site to a Novel Therapeutic Target

“…In MI-induced HF, there is a reparative response to acute ischemic injury since the latter induces cardiomyocyte death. Under these circumstances, there is an acute inflammatory phase to remove necrotic tissue followed by increased collagen production to stabilize cardiac structural integrity at the site of MI injury, although this profibrotic activity often spills into regions remote from the initial injury (Prabhu and Frangogiannis, 2016;Wang et al, 2022). In contrast, in hypertensive heart disease with no obvious acute injury, there is persistent inflammation and oxidative stress that leads to ECM buildup throughout the heart (Berk et al, 2007).…”

“…In contrast, in hypertensive heart disease with no obvious acute injury, there is persistent inflammation and oxidative stress that leads to ECM buildup throughout the heart (Berk et al, 2007). This is exemplified in various reactive cardiac fibrosis models, as recently reviewed (Wang et al, 2022). This so-called reactive fibrosis does not usually have a defining trigger and is a common sequela in hypertension and cardiometabolic disease.…”

“…The ingestion of high salt in the diet is another example of a cardiac fibrotic model, although high salt exerts a variable effect on BP (Wang et al, 2022). In male Wistar rats fed a high-salt diet (8% NaCl), there was a marked hypertensive effect accompanied by modest cardiac fibrosis in the left, but not right, ventricle.…”

Robust Electrochemical Sensors for Detection of Isoprenaline Using Hexagonal Co3O4 Nanoplates Embedded in Few-Layer Ti3C2Tx Nanosheets

“…At present, detection of ISPT in a pharmaceutical formulation or biological matrix is carried out using conventional techniques such as flow-injection analysis, spectroscopic methods, and nuclear magnetic resonance. − Despite their effectiveness, these techniques are restricted to laboratory-scale measurements and require complicated chemical procedures that are often long and tedious . Furthermore, these approaches need a well-maintained infrastructure and are unsuitable for field applications.…”