Nonhuman Primates and Translational Research—Cardiovascular Disease

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Human epidemiological studies provide challenges for understanding mechanisms that regulate initiation and progression of CVD due to variation in lifestyle, diet, and other environmental factors. Studies describing metabolic and physiologic aspects of CVD, and those investigating genetic and epigenetic mechanisms influencing CVD initiation and progression, have been conducted in multiple Old World nonhuman primate (NHP) species. Major advantages of NHPs as models for understanding CVD are their genetic, metabolic, and physiologic similarities with humans, and the ability to control diet, environment, and breeding. These NHP species are also genetically and phenotypically heterogeneous, providing opportunities to study gene by environment interactions that are not feasible in inbred animal models. Each Old World NHP species included in this review brings unique strengths as models to better understand human CVD. All develop CVD without genetic manipulation providing multiple models to discover genetic variants that influence CVD risk. In addition, as each of these NHP species age, their age-related comorbidities such as dyslipidemia and diabetes are accelerated proportionally 3 to 4 times faster than in humans.In this review, we discuss current CVD-related research in NHPs focusing on selected aspects of CVD for which nonprimate model organism studies have left gaps in our understanding of human disease. We include studies on current knowledge of genetics, epigenetics, calorie restriction, maternal calorie restriction and offspring health, maternal obesity and offspring health, nonalcoholic steatohepatitis and steatosis, Chagas disease, microbiome, stem cells, and prevention of CVD.

Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.)

“…Genetically, baboons’ similarity to humans is evidenced at the overall DNA sequence level, individual gene sequence level, as well as chromosomal loci arrangement (Cox et al . ).…”

“…Comparative studies in non‐human primates allow precise environmental control in research subjects to reduce confounds and improved our understanding of the physiology, metabolic features, and genetic and epigenetic mechanisms influencing CVD initiation and progression (Cox et al . ). Specifically, baboons have been used to study glucose metabolism, atherosclerotic plaque formation and hypertension (Vandenberg et al .…”

“…; Cox et al . ). Recent studies suggest that overall heart function declines with ageing in the baboon (Kuo et al .…”

Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta‐analysis of animal studies

“…First, the vast majority of the studies used rodent models. Larger animal models could be of closer parallel to human development . Subgroup analysis of rodents versus other species was only possible for selected outcomes (birth weight, body weight, insulin), due to limited numbers of non‐rodent models.…”

High‐resolution gas chromatography/mass spectrometry metabolomics of non‐human primate serum

“…For over 50 years, baboons ( Papio hamadryas ) have served as an experimental non‐human primate (NHP) model for a wide range of human cardiometabolic disorders owing to their impeccable similarities to humans in genome sequence, pathophysiology (in cardiovascular diseases, obesity, type 2 diabetes), and development . Given the importance of baboons as a NHP model system, we embarked on the investigation described here to capture and analyze serum‐specific metabolites.…”