Lipids and Fatty Acid Metabolism in Cardiovascular Diseases

Dear Colleagues,

This Special Issue aims to provide an in-depth examination of the latest research on cardiovascular diseases (CVDs) and lipid metabolism. CVDs, which encompass a wide range of conditions affecting the heart and blood vessels—such as coronary artery disease, myocardial infarction, heart failure, and cerebrovascular disease—represent a major global health burden due to their high mortality rates, affecting millions of people worldwide. Lipids and fatty acid metabolism play a crucial role in the development, progression, and potential recovery from cardiovascular diseases. Alterations in lipid metabolism are central to the onset and worsening of many CVDs, making this an important area for future discovery. During cardiac development, there is a metabolic shift from glycolysis in the fetal stage to fatty acid (FA) oxidation in the adult heart. This transition is essential because fatty acids provide a more efficient energy source, supporting mitochondrial biogenesis and enabling the heart to meet the increasing energy demands of a growing individual. However, in the context of heart failure and other cardiac diseases, metabolic disturbances—including impaired fatty acid uptake and oxidation—can compromise mitochondrial function, leading to disease progression and complications. Addressing these metabolic imbalances offers a promising avenue for improving patient outcomes. How can we better manage these metabolic shifts and restore healthy fatty acid oxidation in diseased hearts?

Lipid Metabolism in Cardiovascular Disease: Complexities and Opportunities

Changes in lipid metabolism, particularly altered fatty acid oxidation and the buildup of triglycerides, are closely linked to cardiovascular disease complications. However, not all lipids contribute negatively. Certain lipid classes, such as omega-3 long-chain polyunsaturated fatty acids (LC PUFAs), exert protective effects, highlighting the complex relationship between lipid metabolism and cardiovascular health. Omega-3 fatty acids have been shown to improve blood cholesterol profiles, reduce inflammation, regulate heart rhythms, and offer a range of additional cardiovascular benefits. This underscores the importance of distinguishing between lipid species that exacerbate disease and those that offer protective effects. Moreover, lipids are fundamental to the function of endothelial cells, which are crucial for maintaining the integrity of blood vessel walls. Impaired endothelial function, often resulting from dyslipidemia, contributes to the development of atherosclerosis and increases the risk of cardiovascular events. Dyslipidemia—characterized by imbalances in lipid levels—significantly drives the progression of cardiovascular disease, often accompanied by inflammation, which further accelerates conditions like atherosclerosis, potentially leading to heart attacks, strokes, and other serious events.

Advanced Lipid Analysis: A Pathway to Precision Medicine

Recent advances in lipid analysis, particularly through lipidomics, have enabled the identification of lipid biomarkers that are closely associated with cardiovascular disease risk, diagnosis, and prognosis. Lipidomics allows for the comprehensive profiling of lipid species, shedding light on the intricate metabolic changes that occur in cardiovascular conditions. This emerging field holds the potential to transform how we monitor and treat cardiovascular diseases by offering early detection and more accurate prognostic markers.

CVD Prevention Strategies from a Lipid Metabolism Perspective

Dietary Interventions: Promoting the consumption of beneficial lipids—such as omega-3 fatty acids (from fish, flaxseeds, and other sources) and monounsaturated fats (from olive oil and avocados)—while reducing intake of saturated fats and trans fats, is a cornerstone of cardiovascular prevention. Further research into specific lipid-rich foods and their impact on heart health could provide more tailored dietary guidelines. Lipid-Lowering Therapies: While statins have long been a cornerstone of lipid-lowering therapies, newer medications targeting PCSK9, squalene synthase, and other enzymes involved in cholesterol metabolism have shown promise. A detailed examination of the comparative effectiveness of these newer treatments, particularly for individuals with genetic lipid metabolism disorders (such as familial hypercholesterolemia), could refine our approach to managing cardiovascular risk. Anti-inflammatory Lipids: Lipids, particularly those derived from omega-3 fatty acids, play a crucial role in regulating inflammation. Emerging evidence suggests that pro-resolving lipid mediators—like resolvins, protectins, and maresins—could offer new therapeutic strategies for reducing inflammation and preventing cardiovascular events.

Key Lipid Classes for CVD Risk and Biomarker Analysis

Several lipid classes should be prioritized in research to improve our understanding of cardiovascular disease.

Cholesterol and Phospholipids: Cholesterol and phospholipids are essential components of cell membranes and lipid transport systems. Profiling different lipid subtypes, such as HDL, LDL, and VLDL, and understanding their role in cardiovascular health could lead to improved diagnostics and risk assessments. Additionally, investigating lipid peroxidation markers—indicators of oxidative stress—could provide further insights into the molecular mechanisms driving atherosclerosis. Triglycerides: Elevated triglyceride levels, particularly in the context of small, dense LDL particles, are strongly linked to an increased risk of cardiovascular events. Using advanced lipidomic techniques to analyze triglyceride metabolites may reveal biomarkers that track disease progression and provide personalized treatment options.

Sphingolipids and Ceramides: These bioactive lipids are involved in cell signaling, inflammation, and apoptosis, particularly in endothelial cells. Their role in cardiovascular disease, particularly in endothelial dysfunction and atherosclerosis, makes them promising candidates for biomarker discovery and therapeutic targeting. Fatty Acids (FAs): Beyond omega-3 fatty acids, saturated and monounsaturated fatty acids need to be explored in greater depth. Research into short-chain fatty acids (SCFAs), which are produced by gut microbiota, could provide new insights into the gut–lipid–heart axis and its impact on cardiovascular health.

Addressing Altered Fatty Acid Metabolism in Heart Failure

In heart failure, altered fatty acid metabolism—marked by impaired fatty acid uptake and oxidation—can disrupt mitochondrial function, contributing to disease progression. Strategies to address this issue might include those listed below.

Restoring FA Oxidation: Targeting pathways that regulate fatty acid oxidation, such as AMPK (AMP-activated protein kinase) and PPARs (peroxisome proliferator-activated receptors), could help restore efficient energy metabolism in the heart. This may involve the development of beta-oxidation enhancers or PPAR agonists that improve mitochondrial function.

Gene Therapy and Metabolic Modulation: Advances in gene therapy could enable the targeted upregulation of genes involved in fatty acid oxidation and mitochondrial function, offering potential therapeutic benefits for patients with heart failure.

The Future of Lipidomics and Cardiovascular Disease

Recent advances in lipid analysis, particularly through lipidomics, have enabled the identification of lipid biomarkers that are closely associated with cardiovascular disease risk, diagnosis, and prognosis. Lipidomics allows for the comprehensive profiling of lipid species, shedding light on the intricate metabolic changes that occur in cardiovascular conditions. This emerging field holds the potential to transform how we monitor and treat cardiovascular diseases by offering early detection and more accurate prognostic markers.

This Special Issue seeks to highlight the intricate relationship between lipid metabolism and cardiovascular diseases. As we delve into the molecular mechanisms of fatty acid oxidation, lipid signaling, and endothelial function, there are numerous opportunities for discovering novel biomarkers and therapeutic targets. By leveraging the power of lipidomics, dietary interventions, and metabolic modulators, we can better understand, diagnose, and ultimately treat cardiovascular diseases, potentially improving outcomes for millions of patients worldwide.

This Special Issue invites contributions exploring the following key themes:

Lipid Metabolism in Disease Progression and Recovery: The role of altered FA oxidation, triglyceride accumulation, and lipid-induced inflammation in CVDs.

Lipid-Based Prevention Strategies: Dietary interventions, lipid-lowering therapies, and anti-inflammatory lipids for CVD prevention.

Advanced Lipidomic Profiling: The use of lipidomics to identify biomarkers for CVD risk, diagnosis, and prognosis, as well as their potential for precision medicine.

Endothelial Dysfunction and Atherosclerosis: The impact of lipids on endothelial cells and their role in atherosclerosis and other vascular diseases.

Targeting Metabolic Pathways: Potential therapeutic approaches aimed at restoring normal lipid metabolism, improving mitochondrial function, and reducing CVD risk.

We encourage both original research and comprehensive reviews that highlight innovative findings and novel approaches in understanding lipid metabolism’s role in cardiovascular diseases.

Dr. Jasmina Debeljak Martacic
Dr. Tamara Popović
Guest Editors

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• lipid metabolism
• lipidomics
• cardiovascular diseases
• prevention strategies