Background: 

The adipose tissue-derived cytokine adiponectin plays a major role in whole-body energy homeostasis. Adiponectin was shown to be cardioprotective through its vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidative effects in both cardiac and vascular cells. A family of structural and functional adiponectin paralogs was recently discovered and designated as C1q/tumor necrosis factor-alpha-related proteins (CTRPs).

Methods: 

Adult rat cardiomyocytes were stimulated with full-length CTRP1, 2, 7 and 9 or recombinant adiponectin in a time and dose dependent manner. Putative activated signaling cascades (AMPK, ACC) were analyzed by Western Blotting. Cell contractility was examined after short-term (5 min) and long-term (24 h) incubation by electrical stimulation using a cell edge detection system. Furthermore, protective effects of adiponectin and CTRPs were investigated by analyzing cell morphology with Hoechst and Propidium iodide after long-term (24h) treatment with hydrogen peroxide.

Results: 

Adiponectin and most of the investigated CTRPs were able to phosphorylate AMPK at Thr172 and ACC at Ser79. The time course of AMPK and ACC activation, however, was significantly different between adiponectin and the CTRPs. Only mild changes were detected in cell contractility. Adiponectin and CTRP 1, 7 and 9 significantly reduced the number of necrotic cells after exposure to hydrogen peroxide. Pretreatment with the AMPK-inhibitor AraA inhibited these effects.

Conclusions: 

Adiponectin and its paralogs CTRP 1, 7 and 9 may protect the heart against oxidative stress. This protection is dependent on activation of AMPK. Thus, the CTRPs have the potential to play an important role in cardioprotection.