Genetic determinants of lipid metabolism in cardioprotection: From mechanisms to clinical practice
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Mia Manojlovic1, Diana Mahmoud2, Magdalena Pantic3
1University of Novi Sad, Faculty of Medicine in Novi Sad, Novi Sad, Serbia; Clinic for Endocrinology, Diabetes and Metabolic Disorders, University Clinical Center of Vojvodina, Novi Sad, Serbia.
Insights
Genetic variations influencing lipid metabolism offer lifelong protection against cardiovascular disease. Understanding these genetic factors aids in developing targeted therapies and improving risk prediction for atherosclerosis.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Metabolic Disorders
Background:
- Atherosclerotic cardiovascular diseases are a leading global cause of death.
- Lipoprotein metabolism disorders, particularly elevated LDL cholesterol, are key contributors to atherosclerosis.
- Dyslipidemia is a critical, modifiable risk factor for cardiovascular diseases.
Purpose of the Study:
- To review genetic variants impacting lipid metabolism.
- To explore the therapeutic potential of these genetic findings in cardiovascular therapy.
- To highlight the role of genetic determinants in atherosclerosis and hyperlipidemia.
Main Methods:
- Review of genetic epidemiology studies.
- Analysis of genetic variations affecting lipid metabolism.
- Examination of naturally occurring mutations linked to cardioprotection.
Main Results:
- Lifelong low LDL cholesterol due to genetic variations significantly reduces cardiovascular disease risk.
- Genetic studies inform the development of novel lipid-lowering drugs.
- Genetic insights improve prediction of drug responses and side effects.
Conclusions:
- Genetic factors play a crucial role in individual susceptibility to hyperlipidemia and atherosclerosis.
- Identifying cardioprotective genetic determinants can guide future therapeutic strategies.
- Understanding genetic influences on lipid metabolism is vital for cardiovascular disease prevention and management.
Abstract:
Atherosclerotic cardiovascular diseases continue to be the leading causes of morbidity and mortality globally. Disorders of lipoprotein metabolism contribute significantly to the development of atherosclerosis, which begins with the subendothelial retention of plasma-derived apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein (LDL) and its remnants. Elevated LDL cholesterol levels and triglycerides, coupled with low high-density lipoprotein (HDL) cholesterol levels, are critical risk factors for atherosclerotic cardiovascular diseases. Landmark epidemiological studies have identified dyslipidemia as a key modifiable risk factor for these diseases, elucidating the essential role of lipid abnormalities in atherogenesis and highlighting significant opportunities for cardiovascular disease prevention and risk stratification. Genetic epidemiology studies have shown that lifelong low levels of LDL due to genetic variations markedly reduce the risk of atherosclerotic cardiovascular diseases. Recent advancements in lipid-lowering pharmacology are increasingly informed by genetic studies that reveal naturally occurring mutations offering lifelong cardioprotection. Furthermore, these genetic studies have facilitated the development of novel therapeutics and enhanced the prediction of potential side effects, variability in individual drug responses, and improved risk stratification. This narrative review article aims to summarize key genetic variants that influence lipid metabolism and examine their therapeutic potential in cardiovascular therapy. Given the central role of atherosclerosis in determining cardiovascular risk, it is vital to consider lipid metabolism in the context of genetic factors that affect individual susceptibility to hyperlipidemia. Defining cardioprotective genetic determinants is equally important, as it may provide a foundation for therapeutic strategies by emphasizing protective mechanisms.
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