Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

Background: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.

Methods: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.

Selective PPARα Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis.

Ballooning degeneration of hepatocytes is a major distinguishing histological feature of non-alcoholic steatosis (NASH) progression that can lead to cirrhosis and hepatocellular carcinoma (HCC). In this study, we evaluated the effect of the selective PPARα modulator (SPPARMα) pemafibrate (Pema) and sodium-glucose cotransporter 2 (SGLT2) inhibitor tofogliflozin (Tofo) combination treatment on pathological progression in the liver of a mouse model of NASH (STAM) at two time points (onset of NASH progression and HCC survival). At both time points, the Pema and Tofo combination treatment significantly alleviated hyperglycemia and hypertriglyceridemia.

Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMα) in the Metabolic Syndrome: Is Pemafibrate Light at the End of the Tunnel?

Purpose Of Review: Adoption of poor lifestyles (inactivity and energy-dense diets) has driven the worldwide increase in the metabolic syndrome, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH). Of the defining features of the metabolic syndrome, an atherogenic dyslipidaemia characterised by elevated triglycerides (TG) and low plasma concentration of high-density lipoprotein cholesterol is a major driver of risk for atherosclerotic cardiovascular disease. Beyond lifestyle intervention and statins, targeting the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα) is a therapeutic option.

Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMα): New Opportunities to Reduce Residual Cardiovascular Risk in Chronic Kidney Disease?

Purpose Of Review: Chronic kidney disease (CKD) poses a major global challenge, which is exacerbated by aging populations and the pandemic of type 2 diabetes mellitus. Much of the escalating burden of CKD is due to cardiovascular complications. Current treatment guidelines for dyslipidemia in CKD prioritize low-density lipoprotein cholesterol management, but still leave a high residual cardiovascular risk.

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus.

Modulation of rat liver apolipoprotein gene expression and serum lipid levels by tetradecylthioacetic acid (TTA) via PPARalpha activation.

3-Thia fatty acids are modified fatty acids that promote hepatic peroxisome proliferation and decrease serum triacylglycerol, cholesterol and free fatty acid levels in rats. In vivo administration of tetradecylthioacetic acid (TTA) to rats led to a significant decrease in liver apolipoproteins apoA-I, A-II, A-IV, and C-III mRNA levels, and to an increase of liver acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-II, and 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMG-CoA synthase) mRNA levels and activities. By contrast, no significant changes of lipoprotein lipase (LPL) mRNA levels were detected in rat epididymal adipose tissue.

Use of bacterial expression cloning to localize the epitopes for a series of monoclonal antibodies against apolipoprotein B100.

Bacterial expression of apolipoprotein (apo) B cDNA constructs has been used to map a series of monoclonal antibodies (mAbs) to apoB by immunoblotting. In some cases assignments have been confirmed and refined by (i) semipurification of expressed protein, CNBr digestion, and assignment of the immunoreactive fragments; (ii) controlled digestion of the cDNA with the exonuclease Bal31 and bacterial expression of the truncated proteins that result; or (iii) expression of specific segments of cDNA amplified by the polymerase chain reaction. Forty mAbs were mapped to a minimum of 17 separate determinants on apoB.