The Role of Peroxisome Proliferator-Activated Receptor Gamma and Atherosclerosis: Post-translational Modification and Selective Modulators

Abstract

Atherosclerosis is the hallmark of cardiovascular disease (CVD) which is a leading cause of death in type 2 diabetes patients, and glycemic control is not beneficial in reducing the potential risk of CVD. Clinically, it was shown that Thiazolidinediones (TZDs), a class of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are insulin sensitizers with reducing risk of CVD, while the potential adverse effects, such as weight gain, fluid retention, bone loss, and cardiovascular risk, restricts its use in diabetic treatment. PPARγ, a ligand-activated nuclear receptor, has shown to play a crucial role in anti-atherosclerosis by promoting cholesterol efflux, repressing monocytes infiltrating into the vascular intima under endothelial layer, their transformation into macrophages, and inhibiting vascular smooth muscle cells proliferation as well as migration. The selective activation of subsets of PPARγ targets, such as through PPARγ post-translational modification, is thought to improve the safety profile of PPARγ agonists. Here, this review focuses on the significance of PPARγ activity regulation (selective activation and post-translational modification) in the occurrence, development and treatment of atherosclerosis, and further clarifies the value of PPARγ as a safe therapeutic target for anti-atherosclerosis especially in diabetic treatment.

Effects of frog skin peptide temporin-1CEa and its analogs on ox-LDL induced macrophage-derived foam cells

“…Secondly, MAPK signaling pathway can regulate the inflammatory response of foam cells through PPARγ phosphorylation ( Hosooka et al, 2008 ). The post-translational modification of PPARγ, especially phosphorylation modification, plays an important role in the lipid metabolism ( Yang et al, 2022 ; Yin et al, 2022 ). The three frog skin peptides could inhibit MAPK and NF-κB signaling pathways, but it is unclear whether they regulated PPARγ phosphorylation through MAPK signaling pathway, and inhibit the inflammatory response of foam cells, which is worthy of further study.…”

Molecular mechanism of Cuscutae semen–radix rehmanniae praeparata in relieving reproductive injury of male rats induced with tripterygium wilfordii multiglycosides: A tandem mass tag-based proteomics analysis

“…As a common target gene of PPARα and PPARγ, it plays an important role in lipid and fatty acid metabolism (Fortis-Barrera et al, 2020;Grevengoed et al, 2015). ACSL1 was located in the endoplasmic reticulum, mitochondria-related membrane, and cytosol using isotype-specific antibodies but not in other components of mitochondria (Yin et al, 2022). ACSL1 is thought to play an important role in activating fatty acids to synthesize triacylglycerols (TGs).…”

Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study

“…PPARγ also exerts anti-inflammatory, anti-proliferative, and antiatherogenic effects on the vascular wall and immune cells, which can reduce cardiovascular risk. Considering the accumulating evidence, PPARγ has emerged as one of the promising therapeutic targets for cardiovascular disease [ 41 ]. Lobeglitazone displays 12 times higher affinity to PPARγ than other thiazolidinediones [ 12 , 42 ].…”