TABLE 3.
The experimental study characteristics of CTRP9 in cardiovascular disease.
| Disease | Type of study | Materials | Function and molecular mechanism | References |
| Angiogenesis | (1) Animal | (1) Aortic rings isolated from WT C57BL/6 mice | (1) Exerts vasculoprotective effects via the AdipoR1/AMPK/eNOS dependent/NO mediated signaling pathway. | Zheng et al., 2011 |
| (2) Animal | (2) WT mice, CTRP9 KO mice, and eNOS-KO mice | (2) Promotes endothelial cell function and ischemia-induced revascularization through the eNOS-dependent mechanism. | Yamaguchi et al., 2020 | |
| (3) Animal | (3) Left femoral arteries of WT mice were injured by a steel wire. | (3) Attenuates neointimal formation following vascular injury through inhibit VSMC growth via cAMP-dependent mechanism. | Uemura et al., 2013 | |
| Myocardial injury | (1) Animal | (1) WT, CTRP9 KO mice | (1) Protects against acute cardiac damage by suppressing inflammatory reactions through AdipoR1/AMPK signaling. | Kambara et al., 2015 |
| (2) Animal | (2) WT, CTRP9 KO mice | (2) Protects against MI/R injury via activation of the PKA-CREB pathway and inhibiting cardiomyocyte apoptosis. | Zhao D. et al., 2018 | |
| (3) Animal | (3) WT rats | (3) Alleviates inflammation to ameliorate myocardial infarction in rats by activating Nrf2. | Liu et al., 2020 | |
| (4) Animal/ cell line | (4) High-fat diet induced type 2 diabetes model mice; H9c2 cardiac muscle cell line | (4) Downregulation of CTRP9 induces TNF-α-initiated oxidative PPARγ suppression contributes to exacerbated diabetic cardiac injury. | Su et al., 2013 | |
| (5) Animal/ cell line | (5) C57BL/6J mice feed a high fat diet; 3T3-L1 cell line | (5) Enhancing cardiac CTRP9 production attenuates diabetic cardiac injury. | Yuan et al., 2015 | |
| (6) Animal/ Primary cell | (6) Mouse model; Primary cardiac myocytes; 3T3-L1 cells | (6) Protects against acute cardiac injury following ischemia- reperfusion via an AMPK-dependent mechanism. | Kambara et al., 2012 | |
| (7) Animal/ cell line | (7) H9c2 cells; Rats feed a high fat diet | (7) Exerts cardioprotection by reducing ERS in diabetic heart through increasing disulfide-bond A oxidoreductase-like protein | Bai et al., 2016 | |
| (8) Animal | (8) Rats with myocardial infarction | (8) Attenuates atrial inflammation and fibrosis via inhibitory effects on the TLR4/NFκB and Smad2/3 signaling pathway. | Liu et al., 2019a | |
| (9) Animal/ Primary cells | (9) Myocardial infraction rat model; Rat peritoneal macrophages | (9) Modulating M1/M2 macrophage polarization via the TLR/MD2/ MyD88 and AMPK-NFκB pathway. | Liu et al., 2019b | |
| (10) Animal/ Primary cells | (10) CTRP KO mice; Adult ventricular cardiomyocytes | (10) Promotes hypertrophic cardiac remodeling and dysfunction after TAC in mice and induced hypertrophy in isolated adult cardiomyocytes. | Appari et al., 2017 | |
| (11) Animal/ Primary cells | (11) CTRP9 KO mice; Neonatal rat cardiac myocytes | (11) Anti-myocardial lipotoxicity properties and inhibited cardiac hypertrophy through the LKB1/AMPK signalling pathway. | Zuo et al., 2020b | |
| (12) Animal/ Cell line | (12) Mice with myocardial infraction; ADSCs | (12) Maintaining a healthy microenvironment facilitating stem cell engraftment in infarcted myocardial tissue. | Yan et al., 2017; Weng et al., 2019; Du et al., 2020 | |
| Atherosclerosis | (1) Animal/ Cell line | (1) ApoE KO mice; RAW 264.7 cell | (1) Attenuates the development of atherosclerosis and enhances the plaque stability in ApoE KO mice. | Li et al., 2015; Huang et al., 2019 |
| (2) Cell line | (2) RAW 264.7 cell | (2) Showed atheroprotective function via CTRP9-AMPK- NLRP3 inflammasome pathway. | Zhang et al., 2019; Chen et al., 2020a | |
| (3) Cell line | (3) ThP-1 cell | (3) Inhibits THP-1 macrophage foam cell formation by entophagy. | Zhang L. et al., 2018 | |
| (4) Cell line | (4) Endothelial cell | (4) Attenuates palmitic acid-induced endothelial cell senescence via increasing autophagy | Lee et al., 2020 | |
| (5) Cell line | (5) Human aortic VSMCs | (5) Inhibits the cholesterol-induced VSMCs phenotypes switch and cell dysfunction by activating AMP-dependent kinase. | Liu et al., 2017 | |
| (6) Cell co-culture system | (6) ThP-1 cell; VSMCs | (6) Induces macrophages polarization into M1 phenotype through activating JNK pathway and enhances VSMCs apoptosis in macrophages and VSMCs co-culture system. | Chen et al., 2020b | |
| PAH | (1) Animal; Cell line | (1) Human primary pulmonary artery epithelial cells; Rats | (1) Ameliorates PAH through attenuating inflammation and improving endothelial cell survival and function. | Li et al., 2016 |
| (2) Animal; Cell line | (2) HPSMCs; Rats | (2) Regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and migration via TGF-β1/ERK1/2 signaling pathway. | Li et al., 2017 | |
| (3) Animal/ Primary cells | (3) Rats; Adult Cardiomyocytes, Endothelial Cells and Fibroblasts | (3) Mediates cardioprotective effects through inhibition of ROS production induced by pro-hypertrophic agents via AMPK-mediated activation of anti-oxidant enzymes. | Niemann et al., 2020 | |
| (4) Animal | (4) Rats | (4) Mitigate the progression of arteriovenous shunt-induced pulmonary artery hypertension in rats. | Guan et al., 2021 |
AdipR1, adiponectin receptor 1; ADSCs, human adipose derived mesenchymal stem cells; AMPK, AMP-activated protein kinase; CREB, cAMP responsive element binding protein; DsbA-L, disulfide-bond A oxidoreductase-like protein; eNOS, endothelial nitric oxide synthase; ERK1/2, mitogen-activated protein kinase; ERS, endoplasmic reticulum stress; HPSMCs, human pulmonary smooth muscle cells; JNK, c-Jun N-terminal kinase; KO, knock out; LKB1, Serine/Threonine Kinase 11; MD2, Lymphocyte Antigen 96; MI/R, myocardial ischemia/reperfusion; MYD88, MYD88 innate immune signal transduction adaptor; NFκB, nuclear factor-κB; NO, nitric oxide; NLRP3, NLR family pyrin domain containing 3; Nrf2, NFE2 like BZIP transcription factor 2; PAH, pulmonary artery hypertension; PKA, protein kinase cAMP-activated catalytic subunit alpha; PPARγ, peroxisome proliferator activated receptor gamma; ROS, reactive oxygen species; TAC, transverse aortic coarctation; TGF-β1, transforming growth factor beta 1; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor alpha; VSMCs, vascular smooth muscle cells; WT, wild type.