Review
Nutrition & Dietetics
Malgorzata Sidorkiewicz
Summary: The maintenance of cholesterol homeostasis involves complicated processes such as regulation of cholesterol synthesis, dietary uptake, and bile acid synthesis and excretion. Reverse cholesterol transport, mediated by high-density lipoproteins, plays a vital role in transferring cholesterol from non-hepatic cells to the liver for excretion. MicroRNA-33 has been identified as a key regulator of cholesterol homeostasis, impacting both cellular cholesterol efflux and bile metabolism in the liver. Understanding these mechanisms could lead to new perspectives in microRNA-targeted treatment for cholesterol imbalance.
Review
Biochemistry & Molecular Biology
Yasuhiro Endo, Masanori Fujita, Katsunori Ikewaki
Summary: Cardiovascular disease (CVD) is the leading cause of death in Western countries. Recent epidemiology studies have shown a U-shaped relationship between high-density lipoprotein cholesterol (HDL-C) levels and CVD mortality, with increased mortality in patients with extremely high HDL-C levels. HDL-C raising therapy using nicotinic acids or CETP inhibitors has shown limited efficacy in reducing CVD events. As a result, the focus has shifted to evaluating HDL functionality as a novel biomarker for CVD risk. This review provides an overview of the current status and future perspectives on HDL functions, based on findings from basic research and clinical trials.
Article
Biochemistry & Molecular Biology
Olivier Kamtchueng Simo, Hicham Berrougui, Tamas Fulop, Abdelouahed Khalil
Summary: Aging may reduce the ability of HDL to mediate reverse cholesterol transport, while an atherogenic diet can enhance this process. Cholesterol accumulation in the aortas is more pronounced in aged mice, exacerbating susceptibility to diet-induced atherosclerosis. The dysregulation of membrane cholesterol transporters' expression levels contributes to this phenomenon.
Review
Nutrition & Dietetics
Bianca Papotti, Joan Carles Escola-Gil, Josep Julve, Francesco Poti, Ilaria Zanotti
Summary: Reverse cholesterol transport is a physiological mechanism that protects cells from excessive cholesterol accumulation, while dietary lipids may have detrimental effects on cardiovascular health. This review summarizes the mechanisms of action of different types of dietary lipids on various steps of RCT and provides a critical analysis of data from experimental models to clarify their effects on cardiovascular disease.
Review
Biochemistry & Molecular Biology
Xin Su, Guoming Zhang, Ye Cheng, Bin Wang
Summary: It has been shown in studies that chronic inflammatory response is associated with an increased risk of atherosclerotic cardiovascular disease and alterations in high density lipoprotein (HDL) structure and function. Under inflammatory status, levels of HDL-C are reduced and the structure of HDL particles change, impacting their ability in reverse cholesterol transport.
MOLECULAR BIOLOGY REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ilaria Zanotti, Francesco Poti, Marina Cuchel
Summary: HDL plays an antiatherogenic role by accepting cholesterol from cells and promoting reverse cholesterol transport, with cholesterol efflux capacity being associated with cardiovascular risk in various human cohorts. These findings support the protective role of RCT in humans.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Biochemistry & Molecular Biology
Shuhui Wang Lorkowski, Jonathan D. Smith
Summary: High-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with coronary heart disease (CHD), but the causal relationship between HDL and CHD is unclear. Recent studies have challenged the hypothesis that HDL is protective against CHD, but subsequent research suggests that specific HDL characteristics are causally related to decreased CHD. Different aspects of HDL structure and function may better indicate HDL's protective activity against CHD, beyond simply measuring HDL-C levels.
Article
Biochemistry & Molecular Biology
Weila Dong, Karen H. Y. Wong, Youbin Liu, Michal Levy-Sakin, Wei-Chien Hung, Mo Li, Boyang Li, Sheng Chih Jin, Jungmin Choi, Francesc Lopez-Giraldez, Dedeepya Vaka, Annie Poon, Catherine Chu, Richard Lao, Melek Balamir, Irina Movsesyan, Mary J. Malloy, Hongyu Zhao, Pui-Yan Kwok, John P. Kane, Richard P. Lifton, Clive R. Pullinger
Summary: Low levels of HDL-C are associated with increased risk of arteriosclerotic coronary heart disease, and this study found damaging rare variants in the ABCA1 and LDLR genes to be particularly high in individuals with low HDL-C. Numerous damaging variants were also identified in other HDL candidate genes, suggesting a potential new area of interest in HDL genomics.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Johanna F. Schachtl-Riess, Stefan Coassin, Claudia Lamina, Egon Demetz, Gertraud Streiter, Richard Hilbe, Florian Kronenberg
Summary: The study found that the per-well method for measuring CEC had lower rejection rates and coefficients of variation compared to the time zero method, and the use of four controls on each plate improved assay performance for both methods. Additionally, the choice of lysis reagents, cell numbers, and assay setup significantly impact the quality and reliability of CEC quantification.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Cell Biology
Gaetana Napolitano, Gianluca Fasciolo, Maria Teresa Muscari Tomajoli, Alessandro Carlucci, Ester Ascione, Alfonso Salvatore
Summary: High-density lipoprotein (HDL) is an anti-atherosclerotic protein that converts cholesterol into ester form and transports excess cholesterol to the liver. However, when HDL undergoes oxidation, it becomes dysfunctional and contributes to the development of atherosclerosis. In this study, we found that superoxide radicals, produced during early atherosclerosis, directly oxidize HDL and impair the function of its protein component ApoA1. These findings provide insights into the potential mechanism of atherosclerosis development and suggest therapeutic approaches targeting superoxide generation.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Laura Giorgi, Akseli Niemela, Esa-Pekka Kumpula, Ossi Natri, Petteri Parkkila, Juha T. Huiskonen, Artturi Koivuniemi
Summary: This study combines coarse-grained molecular dynamics simulations with complementary experiments to gain mechanistic insight into how apoA-I mimetic peptide 22A and its variants tune LCAT activity in peptide-lipid nanodiscs. Results show that peptide 22A forms transient antiparallel dimers at the rim of nanodiscs, and the removal of C-terminal lysine K22 decreases dimerization tendency and LCAT activity. Furthermore, simulations reveal that LCAT localizes preferentially to the rim of nanodiscs in a manner that shields important domains from water phase, and the conformation of LCAT in the rim affects its activity.
MOLECULAR PHARMACEUTICS
(2022)
Article
Cardiac & Cardiovascular Systems
Marc P. Bonaca, Richard T. George, David A. Morrow, Brian A. Bergmark, Jeong-Gun Park, Liron Abuhatzira, Andrea L. Vavere, Sotirios K. Karathanasis, ChaoYu Jin, Dewei She, Boaz Hirshberg, Judy Hsia, Marc S. Sabatine
Summary: The study demonstrated that multiple ascending doses of MEDI6012 were safe and well tolerated, and significantly increased HDL-C, HDL cholesteryl ester, and total cholesteryl ester levels in a dose-related manner. These findings support the ongoing Phase 2b program investigating MEDI6012 in ST-elevation MI.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Jennifer Hardfeldt, Marica Cariello, Sara Simonelli, Alice Ossoli, Natasha Scialpi, Marilidia Piglionica, Emanuela Pasculli, Alessia Noia, Elsa Berardi, Patrizia Suppressa, Giuseppina Piazzolla, Carlo Sabba, Laura Calabresi, Antonio Moschetta
Summary: This study aimed to investigate the impact of cardiometabolic risk factors on the anti-atherogenic function of HDL particles, revealing associations between cardiometabolic risk and HDL function and maturation, with abdominal obesity identified as a significant contributor to alterations in key metrics of RCT.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Nutrition & Dietetics
Pedro G. S. Braga, Fatima R. Freitas, Andre L. L. Bachi, Gislene R. Amirato, Roberta V. Baroni, Maria Janieire N. N. Alves, Rodolfo P. Vieira, Mauro W. Vaisberg, Marlene N. Aldin, Roberto Kalil Filho, Antonio M. Figueiredo Neto, Nagila R. T. Damasceno, Thauany M. Tavoni, Raul C. Maranhao, Zhen Chen
Summary: This study investigated the effects of regular physical activity on two important functions of HDL, namely cholesterol reception and antioxidant capacity. The results showed that active individuals had higher HDL-C levels, better cholesterol transfer, and more HDL subfractions compared to inactive individuals. Age did not have a significant effect on these functions.
Article
Medicine, General & Internal
Yonghong Luo, Yanhong Guo, Huilun Wang, Minzhi Yu, Kristen Hong, Dan Li, Ruiting Li, Bo Wen, Die Hu, Lin Chang, Jifeng Zhang, Bo Yang, Duxin Sun, Anna S. Schwendeman, Y. Eugene Chen
Summary: miNano is a potential nanoparticle for treating atherosclerosis by dissolving cholesterol crystals and stabilizing plaques to improve the disease.