HDL as Bidirectional Lipid Vectors: Time for New Paradigms
María Luna-Luna1, Eric Niesor2, Óscar Pérez-Méndez1,3
1Department of Molecular Biology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City 14080, Mexico.
Insights
High-density lipoproteins (HDL) may protect arteries not just by removing cholesterol but also by delivering lipids for tissue repair. This new view challenges the traditional reverse cholesterol transport (RCT) model for HDL function.
Area of Science:
- Lipid metabolism
- Cardiovascular science
- Cell biology
Background:
- High-density lipoproteins (HDL) are primarily known for anti-atherogenic properties attributed to reverse cholesterol transport (RCT).
- Epidemiological studies link higher HDL cholesterol to lower coronary artery disease risk.
- Therapeutic strategies increasing HDL cholesterol have not consistently reduced cardiovascular risk, questioning the sole reliance on RCT.
Purpose of the Study:
- To propose a new paradigm for the physiological function of HDL beyond RCT.
- To explore the role of HDL as bidirectional lipid vectors.
- To investigate HDL's involvement in tissue repair and cellular membrane homeostasis.
Main Methods:
- Conceptual review and hypothesis formulation based on existing literature.
- Analysis of apo AI conservation and its implications for HDL function.
- Integration of HDL's role in atherosclerosis, tissue repair, and insulin secretion.
Main Results:
- HDL may function as bidirectional lipid carriers, delivering lipids to tissues for repair and removing excess membrane components.
- HDL-mediated lipid influx is crucial for tissue repair at damage sites, including arteries.
- HDL-mediated lipid efflux is vital for secretory cells, maintaining membrane integrity and function.
Conclusions:
- The cardioprotective role of HDL may extend beyond RCT, involving bidirectional lipid transport.
- HDL's function as a lipid vector is essential for tissue repair and cellular viability.
- This new hypothesis warrants experimental validation to understand HDL's multifaceted physiological roles.
Abstract:
The anti-atherogenic properties of high-density lipoproteins (HDL) have been explained mainly by reverse cholesterol transport (RCT) from peripheral tissues to the liver. The RCT seems to agree with most of the negative epidemiological correlations between HDL cholesterol levels and coronary artery disease. However, therapies designed to increase HDL cholesterol failed to reduce cardiovascular risk, despite their capacity to improve cholesterol efflux, the first stage of RCT. Therefore, the cardioprotective role of HDL may not be explained by RCT, and it is time for new paradigms about the physiological function of these lipoproteins. It should be considered that the main HDL apolipoprotein, apo AI, has been highly conserved throughout evolution. Consequently, these lipoproteins play an essential physiological role beyond their capacity to protect against atherosclerosis. We propose HDL as bidirectional lipid vectors carrying lipids from and to tissues according to their local context. Lipid influx mediated by HDL appears to be particularly important for tissue repair right on site where the damage occurs, including arteries during the first stages of atherosclerosis. In contrast, the HDL-lipid efflux is relevant for secretory cells where the fusion of intracellular vesicles drastically enlarges the cytoplasmic membrane with the potential consequence of impairment of cell function. In such circumstances, HDL could deliver some functional lipids and pick up not only cholesterol but an integral part of the membrane in excess, restoring the viability of the secretory cells. This hypothesis is congruent with the beneficial effects of HDL against atherosclerosis as well as with their capacity to induce insulin secretion and merits experimental exploration.
