High density lipoprotein in atherosclerosis and coronary heart disease: Where do we stand today?

Zvintzou, Evangelia; Karampela, Dimitra Sotiria; Vakka, Aggeliki; Xepapadaki, Eva; Karavia, Eleni A.; Hatziri, Aikaterini; Giannopoulou, Panagiota; Kypreos, Kyriakos E.

doi:10.1016/j.vph.2021.106928

Cited by 11 publications

(6 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to apolipoproteins, HDL proteome includes many other protein components such as PLTP, LCAT, paraoxonase 1 (PON1), myeloperoxidase (MPO), serum amyloid A, (SAA), and platelet activating factor acetylhydrolase (PAF-AH), also known as lipoprotein-associated phospholipase A2 (Lp-PLA2). The presence of these proteins and their relative concentration on each HDL particle affect its functionality [ 1 ].…”

Section: Hdl Proteome and Particle Functionalitymentioning

confidence: 99%

“…Unfortunately, however, the AIM-HIGH (ClinicalTrials.gov: NCT00120289 (accessed on 28 May 2023)) and the HPS2-THRIVE (ClinicalTrials.gov: NCT00461630 (accessed on 28 May 2023)) trials failed to demonstrate the benefit of niacin on cardiovascular morbidity and mortality [89]. This is a highly controversial conclusion given that the level of the quality of clinical evidence from these trials is very low, when evaluated based on the principles of GRADE (grading of recommendations, assessment, development, and evaluations) [1]. The favorable effect of niacin on the lipoprotein profile could be proven beneficial in properly designed clinical trials addressing the weaknesses of AIM-HIGH and HPS2-THRIVE.…”

Section: Current State Of the Art In Hdl Pharmaceuticalsmentioning

confidence: 99%

“…The favorable effect of niacin on the lipoprotein profile could be proven beneficial in properly designed clinical trials addressing the weaknesses of AIM-HIGH and HPS2-THRIVE. For example, niacin could reduce residual cardiovascular risk in patients with hypertriglyceridemia (a population similar to those tested in REDUCE-IT trial, Clinicatrials.gov: NCT01492361 (accessed on 28 May 2023)) [1]. Significant increase in HDL-C levels from 24 mg/dL to a maximum of 65 mg/dL.…”

Section: Current State Of the Art In Hdl Pharmaceuticalsmentioning

confidence: 99%

“…Extensive clinical evidence indicates that low-plasma, high-density lipoprotein (HDL)-cholesterol (HDL-C) levels constitute an important risk factor in coronary heart disease (CHD) development and overall cardiovascular mortality [ 1 ]. Despite the original assumption that HDL-C levels are inversely correlated with cardiovascular (CVD) risk, recent epidemiological studies redefined this relationship, showing that it is “U-shaped” [ 2 ], with the optimal HDL-C levels in the range of 40–70 mg/dL for men and 50–70 mg/dL for women.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities

Zvintzou,

Xepapadaki,

Skroubis

et al. 2023

Pharmaceuticals

Self Cite

View full text Add to dashboard Cite

High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein transport system, best known for its ability to promote the reverse cholesterol efflux and the unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice and humans suggest that HDL may play important novel roles in other physiological processes associated with various metabolic disorders. Important parameters in the HDL functions are its apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional HDL particles contribute to the development of metabolic diseases such as morbid obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle functionality is expected to benefit such pathological conditions. The failure of previous clinical trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on the principle of “the more the better”, ignoring the U-shape relationship between HDL-C levels and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving the functionality of dysfunctional HDL.

show abstract

Section: Hdl Proteome and Particle Functionalitymentioning

confidence: 99%

Section: Current State Of the Art In Hdl Pharmaceuticalsmentioning

confidence: 99%

Section: Current State Of the Art In Hdl Pharmaceuticalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities

Zvintzou,

Xepapadaki,

Skroubis

et al. 2023

Pharmaceuticals

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cardiovascular diseases are the leading cause of death in both type 1 and type 2 diabetes 1 , and diabetic dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Lowering low‐density lipoprotein cholesterol (LDL‐C) with statin therapy effectively reduces cardiovascular risks in people with and without diabetes 2 but substantial residual risks still exist despite the documented benefits of statin 3 . In addition to elevated LDL‐C, a low level of high‐density lipoprotein cholesterol (HDL‐C) is another important risk factor for ASCVD.…”

Section: Introductionmentioning

confidence: 99%

High‐density lipoprotein in diabetes: Structural and functional relevance

Lui,

Tan

2024

J of Diabetes Invest

View full text Add to dashboard Cite

Low levels of high‐density lipoprotein‐cholesterol (HDL‐C) is considered a major cardiovascular risk factor. However, recent studies have suggested a more U‐shaped association between HDL‐C and cardiovascular disease. It has been shown that the cardioprotective effect of HDL is related to the functions of HDL particles rather than their cholesterol content. HDL particles are highly heterogeneous and have multiple functions relevant to cardiometabolic conditions including cholesterol efflux capacity, anti‐oxidative, anti‐inflammatory, and vasoactive properties. There are quantitative and qualitative changes in HDL as well as functional abnormalities in both type 1 and type 2 diabetes. Non‐enzymatic glycation, carbamylation, oxidative stress, and systemic inflammation can modify the HDL composition and therefore the functions, especially in situations of poor glycemic control. Studies of HDL proteomics and lipidomics have provided further insights into the structure–function relationship of HDL in diabetes. Interestingly, HDL also has a pleiotropic anti‐diabetic effect, improving glycemic control through improvement in insulin sensitivity and β‐cell function. Given the important role of HDL in cardiometabolic health, HDL‐based therapeutics are being developed to enhance HDL functions rather than to increase HDL‐C levels. Among these, recombinant HDL and small synthetic apolipoprotein A‐I mimetic peptides may hold promise for preventing and treating diabetes and cardiovascular disease.

show abstract

Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

Bhale,

Meilhac,

d'Hellencourt

et al. 2024

BioFactors

View full text Add to dashboard Cite

High‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named “apo” lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in‐depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation‐based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory‐related disorders.

show abstract

High density lipoprotein in atherosclerosis and coronary heart disease: Where do we stand today?

Cited by 11 publications

References 100 publications

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities

High‐density lipoprotein in diabetes: Structural and functional relevance

Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

Contact Info

Product

Resources

About