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Wang et al. Adipokines in metabolism, and cardiovascular system

the cell migration induced by inflammatory factors [46] . and vascular endothelial cells, but research has been
CTRP9 has been reported to exert positive effects limited on the RNA interference approaches. Solid
on endothelium-dependent vasorelaxation in aortic evidence of the CTRP9 interaction with the adiponectin
vessel ring with the vasorelaxative effects induced receptor on the cell surface is lacking. A yeast-based
via the activation of nitric oxide synthase. Besides assay system for the progestin and adipoQ receptor
that, CTRP9 inhibits the remodeling of vascular wall family (PAQR) receptor activity reveals that the
in the mouse wire-injured model through attenuating adiponectin receptor is identified as the category of
vascular smooth muscle proliferation. It is notable that PAQR1 and PAQR2. Adiponectin is identified as an
those actions have been mediated by CTRP9 through agonist for PAQR3 [52,53] . Since CTRP family members
sharing the adiponectin receptor [47,48] . Those studies share many characteristics with adiponectin, it has
highlight the potential protective roles of CTRPs in been speculated that the CTRP receptors belong to
response to the inflammatory stress. the PAQR family members or share similarity with the
adiponectin receptors.
It has been reported that CTRP3 may act as an
inflammatory molecule to improve the post-ischemic The number of members in the C1q/TNF-related
cardiac function and cardiac remodeling in animal superfamily keeps growing along with the progression
model via the ability to reduce apoptosis. Whereas, of research. C1q engages a broad range of ligands
CTRP6 may affect the inflammatory states in the via its globular domain and modulates cells via the
context of obesity by stimulating the activation of collagen region. The members of this new family are
p42/44 mitogen-activated protein kinase-dependent involved in processes as diverse as inflammation,
pathway [28] . Meanwhile, it can increase the production metabolism, energy conversation/expenditure, and
of anti-inflammatory cytokine IL-10 in monocyte- beyond, including cell differentiation and proliferation.
derived macrophages in human patients. In protecting Therefore, the CTRP family is vastly underestimated
against the inflammatory response of oxidative stress, and its functions need to be further investigated.
CTRP9 can reduce the myocardial ischemia injury-
induced superoxide generation to suppress apoptosis CONCLUSION
and shrink the infarct size [49] . Although CTRP12 has
been reported to be lower in an obese rodent model,
the systemic administration of CTRP12 inhibits the Research on CTRPs has provided insights into their
macrophage pro-inflammatory factor and attenuates metabolic roles and their characteristics of vascular
the infiltration of cells in the obese mice. Hence, protection. Although abundant knowledge has been
CTRP12 not only modulates the glucose homeostasis, gained since the CTRPs were first discovered,
but also leads to the suppression of the inflammatory additional questions still need to be answered.
response of white blood cells [50,51] . CTRPs possess unique and shared functions that
are supported by research using the advanced
Those new investigations and the numerous manipulative techniques, such as the genetic mouse
epidemiological studies indicate that the CTRPs models and gene engineering, and by population
family has the c apabilit y to modulate the research on obese and diabetic patients. Future
metabolic and related inflammation to maintain the studies will reveal novel insights into the physiological
cardiovascular homeostasis. This sheds light on the and pathological functions of CTRPs, their metabolic
biomarker features of CTRPs in the assessment behavior, and possible redundancy of CTRPs in
of obesity relevant diseases or as the therapeutic health and disease. Additionally, studying the CTRPs
link for the treatment of metabolic dysfunction- receptors and the downstream signals that transduce
associated disorders. Even so, large-scale clinical the actions of CTRP in the cell are major challenges
trials to investigate the effects/actions of CTRPs but the research will provide tremendous insights into
on cardiovascular events are required for a better drug design and identification of biomarker.
understanding of the potential risks and beneficial roles
in the prevention of cardiovascular risks. DECLARATIONS

LIMITATIONS Authors’ contributions
Structure design, and finalized the manuscript: Y.J.
Although investigations on the CTRP receptors are Wang
ongoing, much work required to be done to understand Collected data and worked on the revision: W.B. Lau,
them better. Adiponectin receptor1 may in part be X.L. Ma
involved in the effects of CTRP9 on cardiomyocytes Composed the first draft of the article: J.L. Zhao

Vessel Plus ¦ Volume 1 ¦ December 28, 2017 209