The availability of pharmacological approaches able to effectively reduce circulating LDL cholesterol (LDL-C) has led to a substantial reduction in the risk of atherosclerosis-related cardiovascular disease (CVD). However, a residual cardiovascular (CV) risk persists in treated individuals with optimal levels of LDL-C. Additional risk factors beyond LDL-C are involved, and among these, elevated levels of triglycerides (TGs) and TG-rich lipoproteins are causally associated with an increased CV risk. Apolipoprotein C-III (apoC-III) is a key regulator of TG metabolism and hence circulating levels through several mechanisms including the inhibition of lipoprotein lipase activity and alterations in the affinity of apoC-III-containing lipoproteins for both the hepatic receptors involved in their removal and extracellular matrix in the arterial wall. Genetic studies have clarified the role of apoC-III in humans, establishing a causal link with CVD and showing that loss-of-function mutations in the APOC3 gene are associated with reduced TG levels and reduced risk of coronary heart disease. Currently available hypolipidaemic drugs can reduce TG levels, although to a limited extent. Substantial reductions in TG levels can be obtained with new drugs that target specifically apoC-III; these include two antisense oligonucleotides, one small interfering RNA and an antibody.
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http://dx.doi.org/10.1093/cvr/cvad177 | DOI Listing |
Medicine (Baltimore)
December 2024
National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Dyslipidemia has been established as a potential risk factor for venous thromboembolism (VTE) in several observational studies. Statins and novel lipid-modifying agents are being explored for their potential in VTE prevention, encompassing deep vein thrombosis (DVT), and pulmonary embolism (PE). Nonetheless, conclusive evidence supporting the effectiveness remains uncertain.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
Apolipoprotein C3 (APOC3) plays a critical role in regulating triglyceride levels and serves as a key predictor of cardiovascular disease (CVD) risk, particularly in patients with diabetes. While APOC3 is known to inhibit lipoprotein lipase, recent findings reveal its broader influence across lipoprotein metabolism, where it modulates the structure and function of various lipoproteins. Therefore, this review examines the complex metabolic cycle of APOC3, emphasizing the impact of APOC3-containing lipoproteins on human metabolism, particularly in patients with diabetes.
View Article and Find Full Text PDFMed
December 2024
Department of Metabolic Medicine/Chemical Pathology, Guy's & St Thomas' Hospitals, London, UK. Electronic address:
The PALISADE trial extended the data available for inhibition of apolipoprotein (apo) C3 inhibition for treating severe hypertriglyceridemia. 75 patients with persistent chylomicronemia were allocated to 2 doses of plozasiran or placebo. Triglycerides were reduced by a net 53%-58%, and a borderline significant 17% reduction was seen in pancreatitis events.
View Article and Find Full Text PDFEur J Prev Cardiol
December 2024
Metabolism and Lipids Program, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver conditions ranging from simple steatosis to the more severe metabolic dysfunction-associated steatohepatitis (MASH). MASLD is strongly linked to insulin resistance disorders, with a high prevalence among patients with type 2 diabetes. Long-term complications include liver cirrhosis, liver cancer, and cardiovascular disease.
View Article and Find Full Text PDFClin Investig Arterioscler
December 2024
Unidad de Lípidos y Riesgo Cardiovascular, Servicio de Medicina Interna, Complejo Hospitalario Universitario de A Coruña, A Coruña, España. Electronic address:
Familial chylomicronemia syndrome (FCS) is a very rare, underdiagnosed disorder that can cause abdominal pain and recurrent pancreatitis from childhood -potentially life-threatening- and chronic complications such as diabetes mellitus and exocrine pancreatic insufficiency. FCS affects the quality of life and mental health of those who suffer from it, aspects that must be taken into account in its treatment, based on a strict low-fat diet, which is difficult to adhere to and persist. People with FCS lack the lipolytic capacity to hydrolyze triglycerides (TG) and have a minimal or null response to conventional lipid-lowering treatments.
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