HMG-CoA reductase

HMG-CoA reductase inhibitors, commonly known as statins, are the primary treatment choice for cardiovascular diseases, which stand as the leading global cause of mortality. Statins also offer various pleiotropic effects, including improved endothelial function, anti-inflammatory properties, reduced oxidative stress, anti-thrombotic effects, and the stabilization of atherosclerotic plaques. However, the usage of statins can be accompanied by a range of adverse effects, such as the development of type 2 diabetes mellitus, muscular symptoms, liver toxicity, kidney diseases, cataracts, hemorrhagic strokes, and psychiatric complications...

Hypercholesterolemia plays a crucial role in the formation of lipid plaques, particularly with elevated low-density lipoprotein (LDL-C) levels, which are linked to increased risks of cardiovascular disease, cerebrovascular disease, and peripheral arterial disease. Controlling blood cholesterol values, specifically reducing LDL-C, is widely recognized as a key modifiable risk factor for decreasing the morbidity and mortality associated with cardiovascular diseases. Historically, statins, by inhibiting the enzyme β-hydroxy β-methylglutaryl-coenzyme A (HMG)-CoA reductase, have been among the most effective drugs...

3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, HMGCR) is one of the rate-limiting enzymes in the mevalonate pathway required for cholesterol biosynthesis. It is an integral membrane protein of the endoplasmic reticulum (ER) but has occasionally been described in peroxisomes. By co-immunofluorescence microscopy using different HMGCR antibodies, we present evidence for a dual localization of HMGCR in the ER and peroxisomes in differentiated human monocytic THP-1 cells, primary human monocyte-derived macrophages and human primary skin fibroblasts under conditions of low cholesterol and statin treatment...

Sugarcane, a globally cultivated crop constituting nearly 80% of total sugar production, yields residues from harvesting and sugar production known for their renewable bioactive compounds with health-promoting properties. Despite previous studies, the intricate interplay of extracts from diverse sugarcane byproducts and their biological attributes remains underexplored. This study focused on extracting the lipid fraction from a blend of selected sugarcane byproducts (straw, bagasse, and filter cake) using ethanol...

Statins, widely prescribed for lipid disorders, primarily target 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase competitively and reversibly, resulting in reduced low-density lipoprotein cholesterol (LDL-C). This mechanism proves effective in lowering the risk of lipid-related diseases such as ischemic cerebrovascular and coronary artery diseases. Beyond their established use, statins are under scrutiny for potential applications in treating bone diseases. The focus of research centers mainly on simvastatin, a lipophilic statin demonstrating efficacy in preventing osteoporosis and aiding in fracture and bone defect healing...

Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired vascular endothelial function that may be improved by hydroxy-methylglutaryl-CoA (HMG-CoA) reductase enzyme inhibition. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10mg QD) on peripheral vascular function and biomarkers of inflammation and oxidative stress in sixteen patients with HFpEF (Statin: n=8, 74±6 yr, EF 52-73%; Placebo: n=8, 67±9 yr, EF 56-72%)...

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021...

INTRODUCTION: Psoriasis is a chronic, inflammatory, and papulo-squamous skin disorder without a radical cure. Although previous observational analyses have discovered a relationship between medication intake and increased risk of psoriasis, they are susceptible to confounders. OBJECTIVES: We intend to ascertain if there is a causal association between specific medication intake and increased risk of psoriasis by utilizing the Mendelian randomization (MR) method...

BACKGROUND: Hypercholesterolemia and the related inflammatory response promote the development of osteoporosis, but whether targeted interventions are protective against this bone metabolic disease remains unknown. The aim of this study was to investigate the association between the use of statins (one well-recognized cholesterol-lowering drug with anti-inflammatory properties) and the risk of osteoporosis using a drug-targeted Mendelian randomization (MR) approach. METHODS: Instrumental variables predicting three cholesterol-lowering target genes (including HGMCR) and the cholesterol effectors mediated by these genes (i...

Nowadays, it is well recognized that apoptosis, as a highly regulated cellular process, plays a crucial role in various biological processes, such as cell differentiation. Dysregulation of apoptosis is strongly implicated in the pathophysiology of numerous disorders, making it essential to comprehend its underlying mechanisms. One key factor that has garnered significant attention in the regulation of apoptotic pathways is HMG-CoA reductase degradation protein 1, also known as HRD1. HRD1 is an E3 ubiquitin ligase located in the endoplasmic reticulum (ER) membrane...

Red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins, mainly monacolin K) that act by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The European Food Safety Authority (EFSA) assessed the use of RYR and, while pointing out several uncertainties regarding the available data, raised a warning related to the safety of RYR when used as a food supplement at a dose of monacolin as low as 3 mg/day. In their decision in June 2023, EFSA approved the use of monacolins from RYR at doses less than 3 mg/day...

Serial crystallography and time-resolved data collection can readily be employed to investigate the catalytic mechanism of Pseudomonas mevalonii HMG-CoA reductase (PmHMGR) by changing the environmental conditions in the crystal and so manipulating the reaction rate. This enzyme uses a complex mechanism to convert mevalonate to HMG-CoA using the co-substrate coenzyme-A (CoA) and cofactor NAD+ . The multi-step reaction mechanism involves an exchange of bound NAD+ and large conformational changes by a 50-residue subdomain...

The maintenance of cholesterol homeostasis is crucial for normal function at both the cellular and organismal levels. Two integral membrane proteins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and Scap, are key targets of a complex feedback regulatory system that operates to ensure cholesterol homeostasis. HMGCR catalyzes the rate-limiting step in the transformation of the 2-carbon precursor acetate to 27-carbon cholesterol. Scap mediates proteolytic activation of sterol regulatory element-binding protein-2 (SREBP-2), a membrane-bound transcription factor that controls expression of genes involved in the synthesis and uptake of cholesterol...

OBJECTIVES: To investigate the relationship between statin use and coronavirus disease-19 (COVID-19) severity. METHODS: This was a retrospective study of adult patients with confirmed COVID-19 who were hospitalized at Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia. The study was carried out from July - September 2020. Antecedent statin use was evaluated using medication information available in the electronic medical records. RESULTS: In this retrospective study, we collected data from 689 patients hospitalized with COVID-19...

M omordica charantia, Nigella sativa, and Anethum graveolens are established medicinal plants possessing noted anti-diabetic and anti-obesity properties. However, the molecular mechanisms underscoring their inhibitory effects on pancreatic lipase, α-glucosidase, and HMG-CoA reductase remain unexplored. This study aimed to elucidate the efficacy of various NS, MC, and AG blends in modulating the enzymatic activity of pancreatic lipase, HMG-CoA reductase, and a-glucosidase, utilizing an integrative approach combining in vitro assessments and molecular modeling techniques...

Pre-clinical studies in triple negative breast cancer (TNBC) suggest that statins may inhibit cell proliferation, promote cell-cycle arrest, induce apoptosis, change the tumor microenvironment, and improve effectiveness of other therapies. Observational studies have demonstrated variable effects from statin therapy on oncologic outcomes in these patients. As such, we aimed to pool previous data via a systematic review and meta-analysis to elucidate the impact of concurrent statin use on oncologic outcomes for patients with TNBC...

Cadmium, a ubiquitous environmental pollutant, has been implicated in the disruption of various metabolic pathways, contributing to the development of insulin resistance, glucose intolerance, and associated metabolic disorders. This study aimed to investigate the cadmium chloride (CdCl2 ) exposure on metabolic pathways and to assess the potential therapeutic efficacy of the taxifolin-enriched extract in mitigating these disruptions by modulating biochemical pathways. Taxifolin-enriched extract (TEE) was prepared from Pinus roxburghii bark using a green extraction method...

Vitamin D is known to have a positive effect on bone health. Despite the greater frequency of vitamin D deficiency in African Americans (AA), they have a higher bone mineral density (BMD) compared to whites, demonstrating a disconnect between BMD and vitamin D levels in AA. Another intriguing relationship seen in AA is the triglyceride (TG) paradox, an unusual phenomenon in which a normal TG status is observed even when patients house conditions known to be characterized by high TG levels, such as Type II diabetes...

Altered cholesterol metabolism is implicated in brain ageing and Alzheimer's disease. We examined whether key genes regulating cholesterol metabolism and levels of brain cholesterol are altered in dementia and Alzheimer's disease neuropathological change (ADNC). Temporal cortex (n=99) was obtained from the Cognitive Function and Ageing Study. Expression of the cholesterol biosynthesis rate-limiting enzyme HMG-CoA reductase (HMGCR) and its regulator, SREBP2, were detected using immunohistochemistry. Expression of HMGCR, SREBP2, CYP46A1 and ABCA1 were quantified by qPCR in samples enriched for astrocyte and neuronal RNA following laser-capture microdissection...

Hyperphosphatemia or severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection can promote cardiovascular adverse events in patients with chronic kidney disease. Hyperphosphatemia is associated with elevated inflammation and sterol regulatory element binding protein 2 (SREBP2) activation, but the underlying mechanisms in SARS‑CoV‑2 that are related to cardiovascular disease remain unclear. The present study aimed to elucidate the role of excess inorganic phosphate (PI) in SARS‑CoV‑2 N protein‑induced NLRP3 inflammasome activation and the underlying mechanisms in vascular smooth muscle cells (VSMCs)...