Review
Pharmacology & Pharmacy
Kush K. K. Patel, Khosrow Kashfi
Summary: Cholesterol is a vital molecule for maintaining normal physiological homeostasis and serves as a precursor for various substances. However, high cholesterol levels are associated with diseases and cancer progression. Mechanisms for cholesterol-mediated cancer progression include activation of oncogenic signaling pathways and induction of oxidative stress. Lipoprotein molecules HDL and LDL play important roles in this pathogenesis. Some cholesterol-lowering medications may have potential in cancer treatment.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Dongbo Yu, James K. Liao
Summary: This review discusses the development of statins, their non-lipid-lowering benefits, and proposes future research directions in this field.
CARDIOVASCULAR RESEARCH
(2022)
Article
Endocrinology & Metabolism
Man K. S. Lee, Olivia D. Cooney, Xuzhu Lin, Shaktypreya Nadarajah, Dragana Dragoljevic, Kevin Huynh, Danise-Ann Onda, Sandra Galic, Peter J. Meikle, Thomas Edlund, Morgan D. Fullerton, Bruce E. Kemp, Andrew J. Murphy, Kim Loh
Summary: The study revealed that the AMPK/HMGCR axis plays a crucial role in the development of atherosclerosis. Defects in AMPK regulation of HMGCR lead to increased aortic lesions, plaque-associated macrophages, lipid accumulation, and atherogenic monocytes.
MOLECULAR METABOLISM
(2022)
Article
Chemistry, Medicinal
Xing-Zi Li, Shi-You Jiang, Guo-Qiang Li, Qian-Ru Jiang, Jue-Wan Li, Chen-Chen Li, Yu-Qin Han, Bao-Liang Song, Xin-Ran Ma, Wei Qi, Wen-Wei Qiu
Summary: A series of novel HMG499 analogs were synthesized and one of the compounds, 29 (QH536), showed potent activity in promoting HMGCR degradation without inducing cholesterol accumulation in cells. Compound 29 also exhibited effects on lowering cholesterol levels and suppressing various related genes, making it a potential candidate for the treatment of CVD and NASH.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Je-Wen Liou, Hemalatha Mani, Jui-Hung Yen
Summary: Hepatitis is an inflammatory disease of the liver caused by viral infections, most commonly hepatitis B and hepatitis C. Host lipid metabolism, particularly cholesterol metabolism, is crucial for hepatitis viral infection and life cycle. Manipulating host cholesterol metabolism-related genes and proteins, such as using cholesterol-lowering drugs, has shown promising results in the treatment of viral hepatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Medicinal
Tyler Bahr, Gavin Butler, Christian Rock, Kyle Welburn, Kathryn Allred, Damian Rodriguez
Summary: Mono- and sesquiterpenoids are the main chemical constituents of essential oils, which have lipid-lowering properties. Many essential oil compounds have similar effects on cholesterol metabolism, likely through direct agonism of peroxisome-proliferator-activated receptors and direct interaction with sterol-sensing domains. Terpene derivatives in essential oils may have cholesterol-lowering activity and could potentially synergize with statins, but further high-quality studies are needed to establish their clinical efficacy.
PHYTOTHERAPY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Maria Giovanna Lupo, Silvia Marchiano, Maria Pia Adorni, Francesca Zimetti, Massimiliano Ruscica, Maria Francesca Greco, Alberto Corsini, Nicola Ferri
Summary: Overexpression of PCSK9 in rat SMCs led to downregulation of LDL receptor and marker of contractile phenotype. This resulted in increased cell proliferation rate and partial resistance to simvastatin, indicating a potential role of PCSK9 in atherosclerotic plaque development and pharmacological response to statins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Tong-sheng Huang, Teng Wu, Yan-di Wu, Xing-hui Li, Jing Tan, Cong-hui Shen, Shi-jie Xiong, Zi-qi Feng, Sai-fei Gao, Hui Li, Wei-bin Cai
Summary: Huang et al. investigated the effects of long-term statins administration in a mouse model for diabetes and found that it can worsen insulin resistance, renal inflammation and fibrosis. Statins play an important role in the treatment of diabetic nephropathy.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Rebecca Faulkner, Youngah Jo
Summary: Cholesterol is an essential component of cellular membranes and lipoproteins, and also serves as a precursor for steroid hormones and bile acids. The mevalonate pathway, in addition to producing cholesterol, generates nonsterol isoprenoids that are crucial for cell survival. The regulation of the rate-limiting enzyme in the mevalonate pathway, HMGCR, is controlled by a complex feedback regulatory system. Sterols and nonsterol isoprenoids play important roles in transcriptional and post-translational regulation of HMGCR.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Physiology
William J. Griffiths, Yuqin Wang
Summary: This article discusses the concept of accessible plasma membrane cholesterol and its role as a signaling molecule. Accessible cholesterol plays a key role in overall cellular cholesterol homeostasis and provides a second messenger in the hedgehog signaling pathway, as well as potentially serving as a mechanism of resistance to microbial pathogens.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kota Kawamura, Hiromasa Yoshioka, Chikako Sato, Tomoko Yajima, Yuuki Furuyama, Kouji Kuramochi, Kenji Ohgane
Summary: HMG-CoA reductase is a key enzyme in cholesterol biosynthesis, and statins are commonly used inhibitors for treating hyperlipidemia. In this study, we identified a highly potent HMG-CoA reductase degrader, SRP3042, through a structure-activity relationship study. We found that mono-fluorination of tert-butyl groups on the molecule increased degradation activity while reducing lipophilicity, demonstrating the effectiveness of this strategy in balancing potency and physicochemical properties of lead compounds.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biology
Nadeem Ullah Wazir, Irfan Amir Khan, Adil Javed, Taous Khan, Abdul Jabbar
Summary: The study assessed the effect of methanolic root extract of Onosma hispidum in hyperlipidemia and associated vascular dysfunction. The results showed that the extract significantly reduced total triglycerides and cholesterol levels in hyperlipidemic rats and improved vascular dysfunction. This suggests that the extract of Onosma hispidum has a good therapeutic effect on hypercholesterolemia and hypertriglyceridemia.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Plant Sciences
Nourhan Hisham Shady, Ahmed Zayed, Rania Alaaeldin, Mohamed Hisham, Mohamed Gawesh, Randa Mohammed, Mahmoud A. Elrehany, Usama Ramadan Abdelmohsen
Summary: This article focuses on the pathogenesis and pathways involved in hyperlipidemia and summarizes potential drugs derived from natural products. The pharmacological activities and mechanisms of action of phytochemicals extracted from terrestrial plants and their endophytes are discussed based on previous in vivo studies.
SOUTH AFRICAN JOURNAL OF BOTANY
(2023)
Article
Multidisciplinary Sciences
Wanida Sukketsiri, Supawadee Daodee, Supawadee Parhira, Wachirawadee Malakul, Sakara Tunsophon, Nuthathai Sutthiwong, Supita Tanasawet, Pennapa Chonpathompikunlert
Summary: This study aimed to explore the biological properties of passion fruit extracts obtained from the seed and fruit. Analysis showed high contents of piceatannol and polyphenolic stilbene in the seed extract, while beta-carotene and gamma-tocopherol were predominant in the fruit extract. The fruit extract exhibited stronger antioxidant activity and minimal inhibitory effect against HMG-CoA reductase compared to the seed extract. Both extracts showed significant inhibition of lipase and cholesterol esterase activities, and reduction of nitric oxide level in LPS-induced inflammation.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2023)
Review
Pharmacology & Pharmacy
David M. Dolivo, Charlotte R. Reed, Kristine A. Gargiulo, Adrian E. Rodrigues, Robert D. Galiano, Thomas A. Mustoe, Seok Jong Hong
Summary: Fibrosis is a common pathological repair process in organs, but there is a lack of effective therapeutic methods. Repurposing existing drugs, such as statins, can be a complementary strategy to treat tissue fibrosis. Statins have been found to have anti-fibrotic effects through various mechanisms, and a better understanding of these effects can aid in the development of novel therapeutic agents.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Cell Biology
Yunting Zhang, Fan Ying, Xiaoyu Tian, Zhenchuan Lei, Xiao Li, Chun-Yin Lo, Jingxuan Li, Liwen Jiang, Xiaoqiang Yao
Summary: TRPM2 plays a promoting role in the progression of hypercholesterolemia-induced atherosclerosis by linking ROS to Ca2+ and inflammation.
Article
Multidisciplinary Sciences
Chak Kwong Cheng, Xiao Lin, Yujie Pu, Joyce Ka Yu Tse, Yu Wang, Cheng-Lin Zhang, Xiaoyun Cao, Chi Wai Lau, Juan Huang, Lei He, Jiang-Yun Luo, Yu-Tsung Shih, Song Wan, Chi Fai Ng, Li Wang, Ronald Ching Wan, Jeng-Jiann Chiu, Ting Fung Chan, Xiao Yu Tian, Yu Huang
Summary: This study utilized single-cell RNA sequencing to explore the transcriptional landscape and heterogeneity of dysfunctional endothelial cells in atherosclerotic aortae. SOX4 was identified as a novel marker for atherosclerosis and was shown to promote atherogenesis and endothelial-to-mesenchymal transition. Hyperlipidemia-associated cytokines and oscillatory blood flow were found to upregulate SOX4 expression, while the anti-diabetic drug metformin suppressed SOX4 levels in endothelial cells.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Li Wang, Chak Kwong Cheng, Min Yi, Kathy O. Lui, Yu Huang
Summary: Vascular endothelium plays a crucial role in maintaining vascular homeostasis and regulating vascular function through the release of vasoactive molecules. Imbalance between relaxing and contracting factors derived from the endothelium leads to endothelial dysfunction, which is a critical contributor in aging and chronic cardiometabolic disorders. Oxidative stress and inflammation are key players in endothelial dysfunction and are considered as potential targets for intervention in patients with cardiovascular and metabolic diseases.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Lei He, Cheng-Lin Zhang, Qinghua Chen, Li Wang, Yu Huang
Summary: Atherosclerotic vascular disease and its complications are leading causes of mortality globally. Studies have shown that endothelial cells are influenced by low or disturbed shear stress at curvatures and bifurcations in the arterial tree, playing a role in the formation and development of atherosclerotic plaques. Understanding mechanosensitive signaling cascades may offer new translational strategies for therapeutic intervention of atherosclerotic vascular disease.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Qiangqiang Li, Rongliang Wang, Zhe Zhang, Haixing Wang, Xiaomin Lu, Jiajun Zhang, Alice Pik-Shan Kong, Xiao Yu Tian, Hon-Fai Chan, Arthur Chi-Kong Chung, Jack Chun-Yiu Cheng, Qing Jiang, Wayne Yuk-Wai Lee
Summary: Exercise in later life is important for bone health, but the effectiveness may be impaired due to the degeneration of osteocyte activity and lacunocanalicular networks. In this study, it was found that the deletion of Sirt3 in osteocytes could impair the formation of dendritic processes and inhibit bone gain in response to exercise. Mechanistic studies revealed that Sirt3 regulates E11/gp38 through the PKA/CREB signaling pathway. Additionally, the Sirt3 activator honokiol enhanced osteocyte sensitivity and reduced bone loss in aged mice.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Pharmacology & Pharmacy
Huanyu Ding, Minchun Jiang, Chi Wai Lau, Jianfang Luo, Andrew M. M. Chan, Li Wang, Yu Huang
Summary: YAP inhibition by CBL0137 is a promising therapeutic approach for atherosclerotic vascular disease.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Sport Sciences
Xiaoyuan Zhang, Xiao Yu Tian, Masashi Miyashita, Fenghua Sun, Wendy Y. J. Huang, Chen Zheng, Man Kuk Sum, Stephen H. S. Wong
Summary: The study aimed to investigate the effects of individualized accumulated or continuous exercise on postprandial glucose (PPG) control in young adults with obesity. The results showed that both continuous and accumulated exercise reduced PPG, insulin, and C-peptide concentrations, and improved glucose fluctuations. Accumulated exercise maintained lower PPG concentrations for a longer time than continuous exercise in young adults with obesity.
EUROPEAN JOURNAL OF SPORT SCIENCE
(2023)
Article
Agriculture, Multidisciplinary
Jianhui Liu, Huafang Ding, Chi Yan, Zouyan He, Hanyue Zhu, Ka Ying Ma
Summary: The aim of this study was to explore the underlying mechanisms linking the intestinal microbiota and anti-obesity benefits of green tea, oolong tea, and black tea catechins. The results showed that the three tea catechins significantly alleviated obesity and low-grade inflammation, prevented hepatic steatosis, and upregulated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPAR alpha). Metagenomic analysis indicated that the three tea catechins similarly changed the microbiota in terms of overall structure, composition, and protein functions by regulating metabolites and repressing lipopolysaccharides. Therefore, the anti-obese properties of tea catechins were partially mediated by their effects on gut microbiota, hepatic steatosis alleviation, and anti-inflammatory activity.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Genetics & Heredity
Qian He, Kevin Chun Hei Wu, Adam N. Bennett, Beifang Fan, Jundong Liu, Ruixuan Huang, Alice P. S. Kong, Xiaoyu Tian, Man Ki Maggie Kwok, Kei Hang Katie Chan
Summary: This study used a two-sample Mendelian randomisation approach to investigate the relationship between genetic variants and expression or DNA methylation of NSAID target genes. The results revealed that lower expression and DNA methylation of NEU1 in blood were associated with lower CRP levels and decreased risk of MDD. The findings suggest the potential role of NEU1 inhibitors or supplements in the treatment of MDD.
PHARMACOGENOMICS JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Chak Kwong Cheng, Huanyu Ding, Minchun Jiang, Huiyong Yin, Maik Gollasch, Yu Huang
Summary: Perivascular adipose tissue (PVAT) refers to the aggregate of adipose tissue surrounding the vasculature, exhibiting the phenotypes of white, beige and brown adipocytes. PVAT is actively involved in the regulation of reactive oxygen species (ROS) homeostasis and inflammation in the vascular system. The phenotype-genotype of PVAT varies in different regions of the vasculature and plays a role in cardiovascular pathogenesis. Treatments targeting PVAT may provide new therapeutic insights for cardiovascular diseases.
Article
Multidisciplinary Sciences
Chenguang Wang, Yalan Wu, Yangxian Li, Yang Zhang, Yee Lok Fung, Ka Kui Tong, Chi Wai Lau, Li Xiang, Kin Ming Kwan, Li-Ru You, Yu Huang, Xiao Yu
Summary: The study reveals that endothelial Smad4 plays a role in the beiging of white adipose tissue through angiogenesis and the expansion of adipose precursors. Knocking out Smad4 leads to attenuated angiogenesis and proliferation of adipogenic precursors. Furthermore, Smad4 is found to be involved in angiogenesis-related pathways in human endothelial cells.
Article
Cell Biology
Huixian Li, Chufeng He, Ruiwen Zhu, Francis M. Chen, Lin Wang, Fung Ping Leung, Xiao Yu Tian, Gary Tse, Wing Tak Wong
Summary: This study reveals that interleukin-4 (IL-4) and interleukin-13 (IL-13) play a critical role in post-ischemic angiogenesis. Deficiency of IL-4/IL-13 leads to impaired reperfusion and muscle repair in ischemic muscles. Mechanistically, IL-4/IL-13 promote endothelial cell proliferation, migration, and tube formation through the IL-4Ra/STAT6 signaling pathway. Additionally, decreased expression of IL-4/IL-13 is associated with angiogenesis deficit in diabetic peripheral arterial disease (PAD), while IL-4/IL-13 treatment can rescue this defective regeneration.
Article
Sport Sciences
Chen Zheng, Jason M. R. Gill, Feng Hua Sun, Wendy Yajun Huang, Sinead Sheridan, Xiang-Ke Chen, Yalan Wu, Chun-Kwok Wong, Xiao Yu Tian, Stephen Heung-Sang Wong
Summary: Increasing daily physical activity is an effective way to reduce the risk of cardiometabolic diseases. This study compared the effects of increasing light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) on cardiometabolic markers in Chinese adults with obesity. The results showed that MVPA had more positive effects on body composition and cardiometabolic biomarkers compared to LPA.
JOURNAL OF SPORTS SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zouyan He, Hanyue Zhu, Jianhui Liu, Erika Kwek, Ka Ying Ma, Zhen-Yu Chen
Summary: This study found that mangiferin can alleviate TMAO-induced atherosclerosis through its anti-inflammatory, cholesterol-lowering, and gut microbial modulatory activities.
Article
Medicine, Research & Experimental
Huina Zhang, Lu Peng, Yifan Wang, Wen Zhao, Wayne Bond Lau, Yajing Wang, Yu Li, Yunhui Du, Linyi Li, Yu Huang, Shaoping Nie, Yanwen Qin, Xinliang Ma, Yongxiang Wei
Summary: This study reveals the role of circulating extracellular vesicles (EVs) in regulating endothelial function through the delivery of miR-144 to endothelial cells, reducing the expression of nuclear factor erythroid 2-related factor 2. Erythrocytes were identified as the primary cellular source of miR-144-enriched serum-derived EVs, which were largely responsible for endothelial dysfunction induced by chronic intermittent hypoxia. Silencing miR-144 confirmed its essential role in this dysfunction. The findings expand our understanding of blood-borne substances involved in vascular homeostasis and suggest that anti-miR-144-loaded EVs could be a promising therapeutic approach for conditions such as obstructive sleep apnea or chronic intermittent hypoxia-induced endothelial dysfunction.