CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

Abstract

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.

CTRP3 attenuates inflammation, oxidative and cell death in cisplatin induced HK-2 cells

“…Sustained and excessive production of inflammatory cytokine and activation of inflammatory cells aggravate cisplatin-induced kidney damage ( Ozkok & Edelstein, 2014 ). According to our study findings, which were consistent with findings from a study suggesting that CTRP3 overexpression inhibited uric acid-induced inflammation with decreased levels of TNF-α and IL-6 ( Zhang et al, 2022 ), HK-2 cells exposed to cisplatin had lower levels of TNF-α and MCP-1 after treatment with CTRP3. Additionally, we found that CTRP3 overexpression alleviated the effects of cisplatin on the viability and apoptosis of HK-2 cells, consistently, the levels of apoptosis-related proteins Bcl-2 and Bax were reversed, whereas CTRP3 silencing aggravated these effects.…”

CTRP3 regulates NF-κB and TGFβ1/Smad3 pathways to alleviate airway inflammation and remodeling in asthmatic mice induced by OVA

“…31 In addition, Zhang et al revealed that CTRP3 could ameliorate uric acid-stimulated inflammation in vascular endothelial cells. 32 Moreover, Meng et al proved that the CTRP3 content was obviously abridged in the hippocampus of mice with depression, and CTRP3 curbed inflammatory response in depressive mouse model by modulating NF-κB signaling. 33 In addition, CTRP3 participates in the regulation of obesity, metabolic dysfunction, and cardiovascular diseases.…”

Multi-faceted roles of C1q/TNF-related proteins family in atherosclerosis

“…Incremental CTRP3 increased the expression of p-PI3K, p-Akt and p-eNOS, indicating that CTRP3 facilitated the activation of PI3K/Akt/eNOS pathway (47). CTRP3 ameliorated uric acid-induced endothelial inflammation and oxidative stress, possibly by inhibiting TLR4-mediated inflammation and down-regulating oxidative stress (81). Globular form CTRP5 is a novel molecule that leads to vascular EC dysfunction through Nox1-mediated mitochondrial apoptosis in diabetes, which indicates that interventions blocking gCTRP5 may protect diabetic EC function (82).…”