Genetic control of apoprotein A-I and atheroprotection: some insights from inbred strains of mice

Abstract

Purpose of review Previous epidemiological studies and studies in experimental animals have provided strong evidence for the atheroprotective effect of HDL and its major apoprotein, apoA-I. Identification of genetic loci associating apoA-I/HDL with cardiovascular disease is needed to establish a causal relationship. Recent findings Pharmacological interventions to increase apoA-I or HDL cholesterol levels in humans are not associated with reduction in atherosclerosis. GWAS studies in humans and hybrid mouse diversity panel (HMDP) studies looking for genetic variants associated with apoA-I or HDL-cholesterol levels with cardiovascular disease and atherosclerosis have not provided strong evidence for their atheroprotective function. Summary These findings indicate that GWAS and HMDP studies identifying possible genetic determinants of HDL and apoA-I function are needed.

Effects of Interesterified Fats on Lipoprotein Sub Fractions and Hepatic Gene Expressions in a Hamster Model

“…On the other hand, there is no reduction in hepatic APO A1 mRNA (Rudling et al, 2002), suggesting that the two genes may not be coordinately regulated. Plasma HDL cholesterol concentration is positively associated with the concentration of APO A1; thus, APO A1 gene expression may be an important determinant of HDL cholesterol levels (Getz and Reardon, 2017). In humans, SFA rises APO A1 protein and HDL cholesterol concentration, while PUFA decreased HDL cholesterol concentrations (Dorfman et al, 2005;Hatahet et al, 2003;Lichtenstein et al, 1999;Plump, 1994).…”

Comprehensive Integration of Multiple Single-Cell Transcriptomic Data Sets Defines Distinct Cell Populations and Their Phenotypic Changes in Murine Atherosclerosis

“…This study has a number of limitations. Even though ApoE knockout is the most frequent murine model used in the studies investigated here, the biology triggered by different genetic models of hyperlipidemia can be different (summarized in Getz et al 42 ). In our integrated object, the majority of data sets are from the ApoE knockout model, but Pan et al included the Ldr knockout model as well.…”