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Marked effects of novel selective peroxisome proliferator-activated receptor ? modulator, pemafibrate in severe hypertriglyceridemia: preliminary report.

ABSTRACT: BACKGROUND:Currently available treatments have only been partly successful in patients with severe hypertriglyceridemia, including those with high serum triglycerides above 1,000 mg/dL (11.3 mmol/L), who often suffer from acute pancreatitis. Pemafibrate is a novel selective peroxisome proliferator-activated receptor ? modulator (SPPARM?) which has been developed as an affordable oral tablet in Japan. We herein report the first three patients with severe hypertriglyceridemia who were successfully treated with pemafibrate. METHODS:Three patients with fasting serum triglyceride (TG) levels above 1,000 mg/dL (11.3 mmol/L) were treated with pemafibrate (0.2-0.4 mg/day, 0.1-0.2 mg BID). RESULTS:Serum TGs decreased from 2,000-3,000 mg/dL (22.6-33.9 mmol/L) to?

SUBMITTER: Iitake C

PROVIDER: S-EPMC7694943 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Marked effects of novel selective peroxisome proliferator-activated receptor α modulator, pemafibrate in severe hypertriglyceridemia: preliminary report.

Iitake Chie C Masuda Daisaku D Koseki Masahiro M Yamashita Shizuya S

Cardiovascular diabetology 20201127 1

<h4>Background</h4>Currently available treatments have only been partly successful in patients with severe hypertriglyceridemia, including those with high serum triglycerides above 1,000 mg/dL (11.3 mmol/L), who often suffer from acute pancreatitis. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα) which has been developed as an affordable oral tablet in Japan. We herein report the first three patients with severe hypertriglyceridemia who were succ ...[more]

PMID: 33246467

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Project description:BACKGROUND New pharmacological approaches are needed to prevent stent restenosis. This study tested the hypothesis that pemafibrate, a novel clinical selective PPARα (peroxisome proliferator-activated receptor α) agonist, suppresses coronary stent-induced arterial inflammation and neointimal hyperplasia. METHODS AND RESULTS Yorkshire pigs randomly received either oral pemafibrate (30 mg/day; n=6) or control vehicle (n=7) for 7 days, followed by coronary arterial implantation of 3.5 × 12 mm bare metal stents (2-4 per animal; 44 stents total). On day 7, intracoronary molecular-structural near-infrared fluorescence and optical coherence tomography imaging was performed to assess the arterial inflammatory response, demonstrating that pemafibrate reduced stent-induced inflammatory protease activity (near-infrared fluorescence target-to-background ratio: pemafibrate, median [25th-75th percentile]: 2.8 [2.5-3.3] versus control, 4.1 [3.3-4.3], P=0.02). At day 28, animals underwent repeat near-infrared fluorescence-optical coherence tomography imaging and were euthanized, and coronary stent tissue molecular and histological analyses. Day 28 optical coherence tomography imaging showed that pemafibrate significantly reduced stent neointima volume (pemafibrate, 43.1 [33.7-54.1] mm3 versus control, 54.2 [41.2-81.1] mm3; P=0.03). In addition, pemafibrate suppressed day 28 stent-induced cellular inflammation and neointima expression of the inflammatory mediators TNF-α (tumor necrosis factor-α) and MMP-9 (matrix metalloproteinase 9) and enhanced the smooth muscle differentiation markers calponin and smoothelin. In vitro assays indicated that the STAT3 (signal transducer and activator of transcription 3)-myocardin axes mediated the inhibitory effects of pemafibrate on smooth muscle cell proliferation. CONCLUSIONS Pemafibrate reduces preclinical coronary stent inflammation and neointimal hyperplasia following bare metal stent deployment. These results motivate further trials evaluating pemafibrate as a new strategy to prevent clinical stent restenosis.

Dataset Information

Marked effects of novel selective peroxisome proliferator-activated receptor ? modulator, pemafibrate in severe hypertriglyceridemia: preliminary report.

Publications

Marked effects of novel selective peroxisome proliferator-activated receptor α modulator, pemafibrate in severe hypertriglyceridemia: preliminary report.

Similar Datasets

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