2020
DOI: 10.1007/s11883-020-0823-5
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Abstract: Purpose of Review Reduction of serum low-density lipoprotein cholesterol (LDL-C) levels by statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has been shown to significantly reduce cardiovascular events risk. However, fasting and postprandial hypertriglyceridemia as well as reduced high-density lipoprotein cholesterol (HDL-C) remain as residual risk factors of atherosclerotic cardiovascular diseases (ASCVD). To treat patients with hypertriglyceridemia and/or low HDL-C, drug… Show more

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Cited by 67 publications
(105 citation statements)
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References 117 publications
(105 reference statements)
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“…PPARα-related drugs that might be safe in treating DCM Different from conventional fibrates, pemafibrate (K-877, Parmodia™), a novel selective PPARα modulator, is mainly metabolized by the liver [ 150 , 151 ], and is 2500 times effective in activating PPARα than the conventional fibrates [ 41 , 150 ] and having a better triglyceride-lowering activity. One of the mechanisms for lowering triglyceride is that, pemafibrate, through PPARα (Fig.…”
Section: Current Therapeutic Options Related To Pparα For Treating DCmentioning
confidence: 99%
“…Hydrophobic interactions of Groups B and C with the ligand-binding pocket of PPARα increase ligand/receptor binding affinity and the flexibility of Group B confers the stronger “induced fit” conformation with PPARα ( Figure 2 A) [ 89 ]. Binding of pemafibrate with high affinity can induce specific structural transitions of PPARα and recruitment of specific co-factor complexes [ 90 , 91 , 92 ]. Finally, pemafibrate could exert on-target effects of PPARα activation while fenofibrate could show not only on-target but also off-target effects, such as deleterious effects on the renal function ( Figure 2 B) [ 90 , 91 , 92 , 93 ].…”
Section: A Comparison Of Pparα Agonists and Other Oral Therapiesmentioning
confidence: 99%
“…Fibrates also moderately increase blood HDL cholesterol. Mechanistically, the PPARα agonists activate PPARα, promote peroxisomal and mitochondrial FAO, initiate cellular cascade to upregulate lipoprotein lipase, and ultimately cause more efficient catabolism of VLDL and TAG (Lakhia et al, 2018;Cheng et al, 2019;Yamashita et al, 2020).…”
Section: Targeting Mitochondrial Energy Metabolism and Lipotoxicity Imentioning
confidence: 99%
“…Excess fat could be derived from either dysfunctional capacity of adipose lipid storage, or from diet-induced hyperlipidemia (high plasma albumin-bound FFAs and cholesterol), or in the condition of renal dysfunction (as commonly exemplified by renal mass reduction in animal model) and defective insulin signaling. Excess kidney ectopic fat deposition and lipid overload in intracellular organelles could lead to ER stress ( Zhao et al, 2008 ), mitochondria dysfunction ( Vamecq et al, 2012 ; Szeto et al, 2016 ), and lysosomal stress ( Yamamoto et al, 2017 , 2020 ). These alterations could change cellular protective mechanisms such as autophagy, mitophagy, lipophagy and contribute to apoptosis and cell damage.…”
Section: Dyslipidemia and Cellular Lipotoxicity-mediated Kidney Injurmentioning
confidence: 99%
“…This in turn would improve the benefit versus risk balance. This rationale, which has already been used successfully in the development of selective estrogen receptor modulators for breast cancer [ 48 ], underlies the SPPARMα concept [ 49 , 50 •].…”
Section: The Spparmα Concept: Aiming To Improve the Benefit–risk Profmentioning
confidence: 99%