GJA5 and neoplasm: We believe that Cx40 is an excellent therapeutic target for CMD based on the following reasons: (a) there are more myoendothelial gap junctions that are composed of connexins (Cxs) in smaller resistant vessels than in large vessels (62–64), suggesting that Cx40 upregulation could be more effective in small vessels; (b) Cx40 is predominantly expressed in ECs (62, 65), so increased Cx40 expression and activity lead to a specific effect on EC function; and (c) overexpression of Cx40 does not lead to abnormal angiogenesis as shown in tumor tissues (66).