Gender-Specific Associations between Circulating T-Cadherin and High Molecular Weight-Adiponectin in Patients with Stable Coronary Artery Disease

Abstract

Close relationships exist between presence of adiponectin (APN) within vascular tissue and expression of T-cadherin (T-cad) on vascular cells. APN and T-cad are also present in the circulation but here their relationships are unknown. This study investigates associations between circulating levels of high molecular weight APN (HMW-APN) and T-cad in a population comprising 66 women and 181 men with angiographically proven stable coronary artery disease (CAD). Plasma HMW-APN and T-cad were measured by ELISA and analysed for associations with baseline clinical characteristics and with each other. In multivariable analysis BMI and HDL were independently associated with HMW-APN in both genders, while diabetes and extent of coronary stenosis were independently associated with T-cad in males only. Regression analysis showed no significant association between HMW-APN and T-cad in the overall study population. However, there was a negative association between HMW-APN and T-cad (P=0.037) in a subgroup of young men (age <60 years, had no diabetes and no or 1-vessel CAD) which persisted after multivariable analysis with adjustment for all potentially influential variables (P=0.021). In the corresponding subgroup of women there was a positive association between HMW-APN and T-cad (P=0.013) which disappeared after adjustment for HDL. After exclusion of the young men, a positive association (P=0.008) between HMW-APN and T-cad was found for the remaining participants of the overall population which disappeared after adjustment for HDL and BMI. The existence of opposing correlations between circulating HMW-APN and T-cad in male and female patient populations underscores the necessity to consider gender as a confounding variable when evaluating biomarker potentials of APN and T-cad.

Adiponectin-Based Therapeutics for Cancer Treatment

“…Consistently, the vascular dysfunction and ischemia-induced heart problems have been observed in T-cadherin-deficient mice, similar to those of the adiponectindeficient mice [154,156,157]. In human, genetic polymorphisms of CDH13 are significantly associated with various cardiometabolic and vascular phenotypes [144,146,151,154,158,159].…”

“…It acts as an adiponectin receptor and binds to the hexamers and HMW multimers [143]. Due to the lacking of the transmembrane and intracellular domains, T-cadherin is considered to have no direct effects on adiponectin-mediated signal transduction in cells, but regulates the circulating levels and tissue distribution of this adipokine [144,145]. Genetic studies have shown that single nucleotide polymorphisms in CDH13, the gene encoding human T-cadherin, contribute to low levels of adiponectin [146 -151].…”

The Role of Cardiac T-Cadherin in the Indicating Heart Failure Severity of Patients with Non-Ischemic Dilated Cardiomyopathy

“…Functional APN resistance was also demonstrated in the skeletal muscles of patients with chronic HF [49,50] as well as in the myocardium of patients with advanced HF, which regressed after LVAD implantation [41]. Considering the mutual relationship between circulating APN and tissue T-cad, it is plausible that T-cad negatively regulates the circulating levels of APN, inducing APN clearance from blood and sequestering it to the cardiovascular tissues [51]. The diminished expression of T-cad in patients with HF would lead to higher serum levels of APN and be a supplementary mechanism explaining the "adiponectin paradox" [23].…”

Adiponectin circulating levels and 10-year (2002–2012) cardiovascular disease incidence: the ATTICA Study

“…As such, sex and body composition parameters should be taken into account when exploring the association of circulating adiponectin with CVD. Of note, opposing gender-specific associations between circulating HMW adiponectin and circulating T-cadherin levels have been noted in patients with stable coronary artery disease [70]. Moreover, different genotypes of adiponectin could be associated with higher CVD risk in a gender-specific way, since data suggest that the C/C carriers of the rs266729 SNP of adiponectin may have increased CVD mortality risk compared to the C/G or G/G carriers in women, but not in men [71].…”