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High Density Lipoprotein Cholesterol Increasing Therapy: The Unmet Cardiovascular Need.

Cimmino G, Ciccarelli G, Morello A, Ciccarelli M, Golino P - Transl Med UniSa (2014)

Bottom Line: Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial.Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events.As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Italy;

ABSTRACT
Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial. Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events. The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein (CEPT) inhibitors, torcetrapib and dalcetrapib, has led to considerable doubt about the value of the current strategy to raise high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These clinical results, as well as animal studies, have revealed the complexity of HDL metabolism, assessing a more important role of functional quality compared to circulating quantity of HDL. As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation. In this review, we will discuss HDL metabolism and function, clinical-trial data available for HDL-raising agents, and potential strategies for future HDL-based therapies.

No MeSH data available.


Related in: MedlinePlus

Schematic view of RCT: ApoA-I is responsible for the metabolic fate of HDL cholesterol HDLs and is synthesized by the liver. HDLs are released to the circulation as a lipid-poor HDL (nascent HDL), mostly formed by ApoA-I and phospholipids (PL). Through their metabolic maturation, HDLs interact with the ABCA1, ABCG1 and also SR-B1 receptor in the macrophage surface and peripheral tissue increasing their lipid content by taking PLs and cholesterol becoming spherical HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I (SR-BI), for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of reverse cholesterol transport.
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f2-tm-12-29: Schematic view of RCT: ApoA-I is responsible for the metabolic fate of HDL cholesterol HDLs and is synthesized by the liver. HDLs are released to the circulation as a lipid-poor HDL (nascent HDL), mostly formed by ApoA-I and phospholipids (PL). Through their metabolic maturation, HDLs interact with the ABCA1, ABCG1 and also SR-B1 receptor in the macrophage surface and peripheral tissue increasing their lipid content by taking PLs and cholesterol becoming spherical HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I (SR-BI), for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of reverse cholesterol transport.


High Density Lipoprotein Cholesterol Increasing Therapy: The Unmet Cardiovascular Need.

Cimmino G, Ciccarelli G, Morello A, Ciccarelli M, Golino P - Transl Med UniSa (2014)

Schematic view of RCT: ApoA-I is responsible for the metabolic fate of HDL cholesterol HDLs and is synthesized by the liver. HDLs are released to the circulation as a lipid-poor HDL (nascent HDL), mostly formed by ApoA-I and phospholipids (PL). Through their metabolic maturation, HDLs interact with the ABCA1, ABCG1 and also SR-B1 receptor in the macrophage surface and peripheral tissue increasing their lipid content by taking PLs and cholesterol becoming spherical HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I (SR-BI), for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of reverse cholesterol transport.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592041&req=5

f2-tm-12-29: Schematic view of RCT: ApoA-I is responsible for the metabolic fate of HDL cholesterol HDLs and is synthesized by the liver. HDLs are released to the circulation as a lipid-poor HDL (nascent HDL), mostly formed by ApoA-I and phospholipids (PL). Through their metabolic maturation, HDLs interact with the ABCA1, ABCG1 and also SR-B1 receptor in the macrophage surface and peripheral tissue increasing their lipid content by taking PLs and cholesterol becoming spherical HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I (SR-BI), for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of reverse cholesterol transport.
Bottom Line: Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial.Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events.As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Italy;

ABSTRACT
Despite aggressive strategies are now available to reduce LDL-cholesterol, the risk of cardiovascular events in patients with coronary artery disease remains substantial. Several preclinical and clinical studies have shown that drug therapy ultimately leads to a regression of the angiographic lesions but also results in a reduction in cardiovascular events. The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein (CEPT) inhibitors, torcetrapib and dalcetrapib, has led to considerable doubt about the value of the current strategy to raise high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These clinical results, as well as animal studies, have revealed the complexity of HDL metabolism, assessing a more important role of functional quality compared to circulating quantity of HDL. As a result, HDL-based therapeutic interventions that maintain or enhance HDL functionality, such as improving its main property, the reverse cholesterol transport, require closer investigation. In this review, we will discuss HDL metabolism and function, clinical-trial data available for HDL-raising agents, and potential strategies for future HDL-based therapies.

No MeSH data available.


Related in: MedlinePlus