Genetic Lipid Disorders Associated with Atherosclerotic Cardiovascular Disease

Path analysis of the impact of prenatal alcohol on adult vascular function

“…Besides PAE, the other big contributor to impaired microvascular function was hyperlipidemia, which had a direct effect of its own and served as the final point along the path for the indirect effects of dysmorphic features and insulin. Hyperlipidemia is well-known for producing atherosclerosis, which involves the accumulation of lipids, cholesterol, and plaques within the walls of arteries, that reduce blood flow and the delivery of oxygen throughout the body (Mszar et al, 2022). Dietary intake was not assessed in this study so it is not possible to differentiate whether individual differences in lipid metabolism or intake may have contributed to the indirect negative effect of alcohol-related dysmorphic features had on endothelial function.…”

Predicted deleterious variants in ABCA1, LPL, LPA and KIF6 are associated with statin response and adverse events in patients with familial hypercholesterolemia and disturb protein structure and stability

“…LPL encodes a lipase that mediates intravascular hydrolysis of triglycerides packed in triglyceride-rich lipoproteins (chylomicrons and very LDL), and the resulting free fatty acids are delivered to adipose or oxidative tissues as needed [41]. Loss-of-function variants in LPL and other genes involved in triglyceride metabolism can result in severe hypertriglyceridemia, which increases the risk of atherosclerotic CVD [42]. The missense variant LPL rs1801177 (c.106G>A) results in partial defect in LPL catalytic function, and it was reported to be associated with increased risk of CHD [43].…”

Current and Emerging Therapies for Atherosclerotic Cardiovascular Disease Risk Reduction in Hypertriglyceridemia

“…FFA then cross the endothelium for oxidation in skeletal and cardiac muscle or for storage in adipose tissue. Successive rounds of metabolism by LPL yield increasingly dense, more cholesterol rich, and less triglyceride rich particles, termed remnant lipoproteins [ 7 ]. Specifically, chylomicrons are metabolized to chylomicron remnants and VLDL are metabolized to VLDL remnants, then intermediate-density lipoproteins (IDL), and eventually low-density lipoproteins (LDL).…”

“…Recent reports have indicated that severe HTG due to a monogenic disorder occurs with a prevalence of approximately 0.01% in the general population and between 1–2% among all adults with more severe HTG [ 28 , 29 , 30 ]. Genetic testing is generally not recommended for the identification or treatment of HTG given that the genes regulating TG levels are often recessive with heterogeneity in penetrance [ 7 , 31 , 32 ]. However, when a monogenic condition such as familial chylomicronemia syndrome, familial lipodystrophy, and familial dysbetalipoproteinemia is suspected, genetic testing may inform disease prognosis, management strategies, and expectations of lifestyle and pharmacologic response.…”