Journal article

Publication year: 2017

Journal: Basic Research in Cardiology

Volume number: 112

Issue number: 6

ISSN: 0300-8428

eISSN: 1435-1803

Open access status: Hybrid

DOI Link: https://doi.org/10.1007/s00395-017-0650-1

Publisher: Springer

Abstract: 
Recent studies have documented that oxidized low-density lipoprotein cholesterol (oxLDL) levels directly impact myocardial structure and function. However, the molecular mechanisms by which oxLDL affects cardiac myocytes are not well established. We addressed the question whether oxLDL modifies load-free cell shortening, a standardized readout of cardiac cellular function, and investigated whether proprotein convertase subtilisin/kexin-9 (PCSK9) is involved on oxLDL-dependent processes. Adult rat ventricular cardiomyocytes were isolated and incubated for 24 h with oxLDL. PCSK9 was silenced by administration of siRNA. Load-free cell shortening was analyzed via a line camera at a beating frequency of 2 Hz. RT-PCR and immunoblots were used to identify molecular pathways. We observed a concentration-dependent reduction of load-free cell shortening that was independent of cell damage (apoptosis, necrosis). The effect of oxLDL was attenuated by silencing of oxLDL receptors (LOX-1), blockade of p38 MAP kinase activation, and silencing of PCSK9. oxLDL increased the expression of PCSK9 and caused oxidative modification of tropomyosin. In conclusion, we found that oxLDL significantly impaired contractile function via induction of PCSK9. This is the first report about the expression of PCSK9 in adult terminal differentiated ventricular cardiomyocytes. The data are important in the light of recent development of PCSK9 inhibitory strategies.

Harvard Citation style: Schlueter, K., Wolf, A., Weber, M., Schreckenberg, R. and Schulz, R. (2017) Oxidized low-density lipoprotein (oxLDL) affects load-free cell shortening of cardiomyocytes in a proprotein convertase subtilisin/kexin 9 (PCSK9)-dependent way, Basic Research in Cardiology, 112(6), Article 63. https://doi.org/10.1007/s00395-017-0650-1

APA Citation style: Schlueter, K., Wolf, A., Weber, M., Schreckenberg, R., & Schulz, R. (2017). Oxidized low-density lipoprotein (oxLDL) affects load-free cell shortening of cardiomyocytes in a proprotein convertase subtilisin/kexin 9 (PCSK9)-dependent way. Basic Research in Cardiology. 112(6), Article 63. https://doi.org/10.1007/s00395-017-0650-1