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Wang et al. Adipokines in metabolism, and cardiovascular system

disposal in response to glucose challenge in animal levels of CTRPs are negatively correlated with the
models, but also augments local inflammation by severity of CVDs without or with obesity in animals.
targeting the inflammatory cells in production of TNF-α Clinic studies indicate close association between
and IL-10 [28] . Circulating inflammatory cytokines and CTRPs levels and CVDs. Conversely, the expression
pro-inflammatory macrophages were suppressed in of inflammatory mediators in human tissues has been
[5]
the CTRP6-deficient mouse . In addition, CTRP6 observed to be inversely regulated related to the levels
exhibits an immune-regulatory role in the complement of CTRPs [13,39] . Hence, the reciprocal relationship
system as it specifically suppresses the alternative among CTRPs and the inflammatory mediators may
pathway by binding of the finalizing factor-B to treat present a dynamic crosstalk in the development of
arthritis [29] , where CTRP6 displays ability to cure the obesity and diabetic complications. Furthermore, the
arthritis by intra-articulate injection in mice model [29] . dysregulated production of CTRPs shown in obesity is
associated with the pathogenesis of CVDs [40] .
Differing from CTRP6, other CTRPs exhibit the
inflammatory regulatory role in a distinct way. In In contrast to adiponectin, which is a well-established
contrast to suppression of CTRP6 expression by adipokine for its anti-inflammatory and insulin
cytokines, cytokines IL-1β and TNF-α elevate the sensitizer characteristics, CTRPs show diverse
expression of CTRP1 adaptively in the adipose biological activities in the setting of normal metabolic
tissue by which CTRP1 suppresses inflammation [30] . condition and CVDs [Figure 2]. In the past decades,
Meanwhile, CTRP1 impedes collagen-induced platelet adiponectin has been recognized as a member of
coagulation, indicating its potent therapeutic value for the CTRP family as it contains the collagen tail and
treating vascular disorders during the inflammatory C1q like globular domain. Recent studies reported
process [31] . CTRP3 has been shown to be capable that CTRPs exhibit stronger effective and sensitive
of decreasing the secretion of pro-inflammatory response than adiponectin to different CVDs.
mediators by primary human leukocytes, suggesting Therefore, in this section, we mainly focus on the
strongly an anti-inflammatory function, comparable characteristics of anti-inflammatory and metabolic
to adiponectin [32-34] . CTRP5 appears to be a better regulatory actions of the CTRPs in the onset of
biomarker than CTRP3 for predicting the severity of metabolic dysfunction-related CVDs.
obstruction of airflow and systemic inflammation in
patients with COPD although concentration alteration Cardiovascular metabolism plays a pivotal role in
in response to the obese women [35,36] . CTRP4 can the CVDs and the metabolic cascade is particularly
modulate tumor-promoting inflammation in cancer [37] . important to investigate in the normal and disease
CTRP12 has been identified as an anti-inflammatory processes. Cardiovascular metabolic dysfunction
molecule by Enomoto et al. [38] in 2013. Even among contributes to the progression of obesity-linked
the diverse types of cells, CTRP12 exhibits similar cardiovascular events and marks the fate of treatment
anti-inflammatory actions through the MAPK/JNK- application. Accumulating studies show that increased
dependent regulatory pathway to modulate TNF-α levels of CTRP1 are closely associated with the
production. initiation and severity of the coronary arterial disease
and can serve as a marker for myocardial infarction [10] .
Various CTRPs exert beneficial actions on the obesity- Meanwhile, the inhibition of CTRP1 may slow down
associated complications including inflammatory the pathogenesis of early stage atherosclerosis and
disorders through their anti-inflammatory actions. But, prevent the development of pathological vascular
numerous functional, physiological, and mechanistic remodeling [41,42] . Circulating levels of CTRP 3 is elevated
questions regarding the role of CTRPs in inflammation in patients with dysfunction of glucose metabolism and
remain to be answered. The establishment and is associated with numerous cardiovascular metabolic
availability of transgenic and knock-out mice models risk factors [26] . It also can serve as a biomarker to
for investigating inflammatory response of CTRPs will predict proliferative retina disorder (PDR) and has
advance the knowledge of functions and mechanisms beneficial actions for preventing CVDs, providing a
of action of CTRPs. Meanwhile, the receptor(s) promising strategy of vascular remodeling [43] . The
responsible for the CTRP-mediated signal transduction levels of CTRP5 are associated with in-stent restenosis
should be thoroughly characterized and established.
after percutaneous coronary intervention (PCI) with
drug-eluting-stent implantation. CTRP9 can reflect the
CTRPS AND CARDIOVASCULAR SYSTEM pathophysiology of renal involvement and abnormal
glucose metabolism besides impairing vasorelaxation
Reports show that CTRPs have beneficial function in in type 2 diabetics [44] . CTRP15, a newly identified
the CVS and it is well established that the circulating myokine, can link skeletal muscle to lipid homeostasis

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