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)
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)
Article
Multidisciplinary Sciences
Miaoqing Hu, Fan Yang, Yawen Huang, Xin You, Desheng Liu, Shan Sun, Sen-Fang Sui
Summary: NPC1L1 protein is crucial in intestinal cholesterol absorption, and ezetimibe can inhibit NPC1L1 to reduce cholesterol uptake. Cryo-electron microscopy structures revealed that SSD in NPC1L1 responds to alterations in cholesterol levels by binding different numbers of cholesterol molecules, with ezetimibe binding causing inhibition of NPC1L1 function through deformation of the SSD.
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)
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)
Article
Multidisciplinary Sciences
Min Hee Kim, Eun-Ji Lee, Su-Jeong Kim, Yun-Jae Jung, Woo-Jae Park, Inkeun Park
Summary: Macrophage inhibitory cytokine 1 (MIC-1) affects bile acid metabolism and gallstone formation by reducing expression of key cholesterol metabolism regulators, increasing AMPK phosphorylation, and upregulating ABCG5 and ABCG8 expression. This study provides insights into the mechanisms through which MIC-1 influences gallstone formation.
Review
Food Science & Technology
Kaihui Cao, Kaiping Zhang, Muran Ma, Junjie Ma, Jianjun Tian, Ye Jin
Summary: Lactobacillus, as a normal flora in the gut, plays a significant role in regulating metabolism and cholesterol content in the human body by mediating the expression of genes involved in cholesterol synthesis, metabolism, and absorption. This can help inhibit cholesterol absorption and maintain human health.
FOOD SCIENCE & NUTRITION
(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)
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
Biochemistry & Molecular Biology
Mhamed Ramchoun, Tarik Khouya, Eid Alabed Alibrahim, Abdelbassat Hmidani, Khalid Sellam, Souliman Amrani, Hicham Harnafi, Mohamed Benlyas, Fatima Kasbi Chadli, Khadija Ouguerram, Chakib Alem
Summary: Thymus atlanticus extract is effective in alleviating chronic hyperlipidaemia by acting as a cholesterol biosynthesis inhibitor.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Oncology
Lulu Sun, Huan Ding, Yiming Jia, Mengyao Shi, Daoxia Guo, Pinni Yang, Yu Wang, Fanghua Liu, Yonghong Zhang, Zhengbao Zhu
Summary: Genetically proxied inhibition of HMG-CoA reductase and NPC1L1 is associated with lower odds of breast cancer, while genetically proxied inhibition of PCSK9 is associated with reduced risk of prostate cancer.
BREAST CANCER RESEARCH
(2022)
Article
Nutrition & Dietetics
Leah G. Gillingham, Scott V. Harding, Todd C. Rideout, Natalia Yurkova, Stephen C. Cunnane, Peter K. Eck, Peter J. H. Jones
AMERICAN JOURNAL OF CLINICAL NUTRITION
(2013)
Article
Nutrition & Dietetics
Lin Lin, Todd Rideout, Natalia Yurkova, Haifeng Yang, Peter Eck, Peter J. H. Jones
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE NUTRITION ET METABOLISME
(2013)
Review
Cardiac & Cardiovascular Systems
Helena Gylling, Jogchum Plat, Stephen Turley, Henry N. Ginsberg, Lars Ellegard, Wendy Jessup, Peter J. Jones, Dieter Luetjohann, Winfried Maerz, Luis Masana, Guenther Silbernagel, Bart Staels, Jan Boren, Alberico L. Catapano, Guy De Backer, John Deanfield, Olivier S. Descamps, Petri T. Kovanen, Gabriele Riccardi, Lale Tokgozoglu, M. John Chapman
Article
Nutrition & Dietetics
I. Lenoir-Wijnkoop, P. J. Jones, R. Uauy, L. Segal, J. Milner
BRITISH JOURNAL OF NUTRITION
(2013)
Review
Biochemical Research Methods
Dylan S. Mackay, Peter J. H. Jones, Semone B. Myrie, Jogchum Plat, Dieter Luetjohann
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2014)
Article
Biochemistry & Molecular Biology
Vanu R. Ramprasath, Peter J. H. Jones, Donna D. Buckley, Laura A. Woollett, James E. Heubi
LIPIDS IN HEALTH AND DISEASE
(2013)
Article
Biochemistry & Molecular Biology
Vanu R. Ramprasath, Inbal Eyal, Sigalit Zchut, Peter J. H. Jones
LIPIDS IN HEALTH AND DISEASE
(2013)
Article
Biochemistry & Molecular Biology
Vanu R. Ramprasath, Inbal Eyal, Sigalit Zchut, Peter J. H. Jones
LIPIDS IN HEALTH AND DISEASE
(2014)
Article
Biochemistry & Molecular Biology
Todd C. Rideout, Vanu Ramprasath, John D. Griffin, Richard W. Browne, Scott V. Harding, Peter J. H. Jones
LIPIDS IN HEALTH AND DISEASE
(2014)
Review
Nutrition & Dietetics
Christopher P. F. Marinangeli, Peter J. H. Jones
NUTRITION RESEARCH REVIEWS
(2013)
Review
Nutrition & Dietetics
Lin Lin, Hanja Allemekinders, Angela Dansby, Lisa Campbell, Shaunda Durance-Tod, Alvin Berger, Peter J. H. Jones
Review
Food Science & Technology
A. T. Girgih, S. B. Myrie, R. E. Aluko, P. J. H. Jones
TRENDS IN FOOD SCIENCE & TECHNOLOGY
(2013)
Article
Peripheral Vascular Disease
Valerie Carnovale, Marie-Eve Paradis, Iris Gigleux, Vanu R. Ramprasath, Patrick Couture, Peter J. Jones, Benoit Lamarche, Charles Couillard
Article
Food Science & Technology
Mandana Amir Shaghaghi, Scott V. Harding, Peter J. H. Jones
JOURNAL OF FUNCTIONAL FOODS
(2014)