CC Chemokine Receptor 2 Functions in Osteoblastic Transformation of Valvular Interstitial Cells

Background: Calcific aortic valve disease (CAVD) emerges as a challenging clinical issue in older adults. However, the progression of CAVD as well as its mechanism of action is poorly understood. Clinical relevance shows that C-C motif chemokine receptors potentially involved in calcification pathological process of cardiovascular system, but their roles in CAVD are undetermined. Method: Differentially expressed genes were analyzed between CAVD and normal aortic valve tissue samples. CCR2 as well as osteoblastic markers were evaluated in a cohort of CAVD patient. Besides, aortic valvular interstitial cells (AVICs) were separated and cultured to determine the role of CCR2 as well as its mechanism of action in CAVD in vitro. Funding: In this study, we found that CCR2 was elevated in calcified aortic valve clinical specimen and CCR2 was up-regulated in pro-calcifying medium induced AVICs. Blockade of CCR2 by pharmaceutical inhibitor or CCR2 knockdown by siRNA alleviated calcific transformation of AVICs and inhibited the expression of osteoblastic markers including Runx2 and BMP2. Besides, we found that CCR2 exerts its regulation roles in CAVD through PI3-K/Akt pathway. Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: All experiments were approved by the institutional Ethics Committee at Sun-Yat-Sen medical university.