Angiotensin II (Ang II), an effective component of renin-angiotensin system, plays a pivotal role in cardiac
fibrosis, which may further contribute to heart failure. Single-stranded DNA-binding protein 1 (SSBP1), a DNA
damage response protein, regulates both mitochondrial function and extracellular matrix remodeling. In this
study, we aim to investigate the role of SSBP1 in cardiac fibrosis that is induced by Ang II. We infused C57BL/
6J mice with vehicle or Ang II and valsartan using implanted osmotic mini-pumps. Moreover, heart function
was examined by echocardiography and cardiac fibrosis was analyzed via picrosirus red staining. The expression
of COL1A1, COL3A1, SSBP1, p53, Nox1, and Nox4 was analyzed via qRT-PCR and/or immunoblots.
The SSBP1 expression was manipulated via SSBP1 shRNA and pcDNA3.1/SSBP1 plasmids, while the p53 expression
was enhanced via AdCMV-p53 infection. The exposure to Ang II increased the mouse heart weight,
systolic blood pressure, interventricular septal thickness diastolic (IVSTD) and left ventricular end posterior
wall dimension diastolic (LVPWD), which were counteracted by valsartan. While cardiac fibrosis was induced
with Ang II treatment, it was relieved using valsartan. Furthermore, Ang II treatment caused mitochondrial dysfunction,
oxidative stress, and down-regulated SSBP1 expression. The knockdown of SSBP1 increased cardiac
fibroblast proliferation, collagen expression, and decreased p53 expression, which was impeded via SSBP1
overexpression. Moreover, the forced expression of p53 abated the fibroblast proliferation and collagen expression
that was induced by Ang II. To summarize, SSBP1 was down-regulated by Ang II and implicated in cardiac
fibroblast proliferation and collagen expression partly via the p53 protein.

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