Animal models of human atherosclerosis: current progress

Abstract

Atherosclerosis retains the leading position among the causes of global morbidity and mortality worldwide, especially in the industrialized countries. Despite the continuing efforts to investigate disease pathogenesis and find the potential points of effective therapeutic intervention, our understanding of atherosclerosis mechanisms remains limited. This is partly due to the multifactorial nature of the disease pathogenesis, when several factors so different as altered lipid metabolism, increased oxidative stress, and chronic inflammation act together leading to the formation and progression of atherosclerotic plaques. Adequate animal models are currently indispensable for studying these processes and searching for novel therapies. Animal models based on rodents, such as mice and rats, and rabbits represent important tools for studying atherosclerosis. Currently, genetically modified animals allow for previously unknown possibilities in modelling the disease and its most relevant aspects. In this review, we describe the recent progress made in creating such models and discuss the most important findings obtained with them to date.

Toward the Effective Bioengineering of a Pathological Tissue for Cardiovascular Disease Modeling: Old Strategies and New Frontiers for Prevention, Diagnosis, and Therapy

“…Mice, hamsters, rats, rabbits, guinea pigs, and lately pigs have been used as small or large models to investigate chronic atherosclerosis progression as previously reviewed ( 19 , 136 – 140 ). In several animal models, species propensity to spontaneously develop atherosclerosis and/or feeding with cholesterol-rich diets have been exploited to induce or accelerate the development of atherosclerotic lesions in experimental settings.…”

“…Rabbits are the second mammalian species mostly utilized in atherosclerosis modeling thanks to the higher phylogenetic and metabolic proximity to humans than mice. However, the reduced levels of hepatic lipase and hepatotoxicity after high-fat feeding, accompanied by the absence of plasmatic apoA-II and potent inflammatory response render this animal model dissimilar to humans and with more limited application than mice ( 137 , 140 ). Inbreed selection of a Watanabe heritable hyperlipidemic strain with spontaneous hypercholesterolemia and genetic engineering for lipoprotein lipase, apoA-II, and hepatic lipase has partially overcome these limitations ( 137 , 155 – 158 ).…”

Study of Antiatherosclerotic and Endothelioprotective Activity of Peptide Agonists of Epor/Cd131 Heteroreceptor

“…Данная модель отражает одно из ключевых звеньев в патогенезе атеросклероза -оксидативный стресс на фоне митохондриальной дисфункции. Тем не менее, в любой животной модели атеросклероза, индивидуальные различия в сроках и степени формирования бляшек настолько велики, что для тестирования препаратов нужны очень большие группы животных [21][22][23]. В этой связи мы решили стандартизировать процесс атерогенеза путем индукции атеросклероза баллонной травмой и западной диетой.…”

Recent Application of Zebrafish Models in Atherosclerosis Research

“…The disadvantages of these models include long modeling times, high cost, complex experimental procedures, and difficulties in obtaining large amounts of data ( Lee et al, 2017a ). Small mammalian animals such as rabbits and mice are cheaper to rear, and mice can be easily manipulated genetically ( Mushenkova et al, 2019 ; Poznyak et al, 2020 ). However, long-term fat-fed rabbits are prone to hepatotoxicity and a severe inflammatory response, and the plasma lipid profiles differ considerably among inbred strains of mice and also among different mouse mutants, rendering large variation in their susceptibility to AS ( Paigen et al, 1985 ; Getz and Reardon, 2012 ; Fan et al, 2015 ; Golforoush et al, 2020 ; Vedder et al, 2020 ).…”