Zbtb20 deficiency causes cardiac contractile dysfunction in mice. Issue 10 (26th August 2020)

• Record Type: Journal Article
• Authors: Ren, An‐Jing; Chen, Chao; Zhang, Sha; Liu, Mengna; Wei, Chunchun; Wang, Kai; Ma, Xianhua; Song, Yao; Wang, Rui; Zhang, Hai; Chen, Yu‐Xia; Wu, Hong; Xie, Zhifang; Zhang, Youyi; Zhang, Weiping J.
• Is Part Of: FASEB journal. Volume 34:Issue 10(2020)
• Page Start: 13862
• Page End: 13876
• Publication Date: 2020-08-26
• Subjects: blood pressure -- cardiomyocyte -- contractility -- knockout -- mitochondrion -- transcription factor; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202000160RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: The zinc‐finger protein ZBTB20 regulates development and metabolism in multiple systems, and is essential for postnatal survival in mice. However, its potential role in the cardiovascular system remains undefined. Here, we demonstrate that ZBTB20 is critically involved in the regulation of cardiac contractility and blood pressure in mice. At the age of 16 days, the relatively healthy Zbtb20‐null mice exhibited hypotension without obvious change of heart rate or other evidence for heart failure. Moreover, Zbtb20 deletion led to a marked reduction in heart size, left ventricular wall thickness, and cell size of cardiomyocytes, which was largely proportional to the decreased body growth. Notably, echocardiographic and hemodynamic analyses showed that cardiac contractility was greatly impaired in the absence of ZBTB20. Mechanistically, ZBTB20 deficiency decreased cardiac ATP contents, and compromised the enzyme activity of mitochondrial complex I in heart as well as L‐type calcium current density in cardiomyocytes. Furthermore, the developmental activation of some mitochondrial function‐related genes was significantly attenuated in Zbtb20‐null myocardium, which included Hspb8, Ckmt2, Cox7a1, Tfrc, and Ogdhl. Put together, these results suggest that ZBTB20 plays a crucial role in the regulation of heart development, energy metabolism, and contractility.