Overexpression of angiotensin-converting enzyme 2 inhibits angiotensin II type 1 receptor expression and signal transducer and activator of transcription 3 phosphorylation in cultured smooth muscle cells / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of recombinated lentiviral angiotensin-converting enzyme 2 (ACE2) vector transfer on the expression of angiotensin II type 1 (AT1) receptor in cultured vascular smooth muscle cells (VSMCs).</p><p><b>METHODS</b>VSMCs were divided into 7 groups (1) CONTROL serum-free culture medium; (2) Lentiviral-GFP vector group Lentiviral-GFP vector (MOI = 10); (3) Ang II group (10(-7) mol/L); (4) Ang II (10(-7) mol/L) + Lentiviral-ACE2 (MOI = 10) group; (5) Ang II (10(-7) mol/L) + Irbesartan (10(-7) mol/L) group ; (6) Ang II (10(-7) mol/L) + irbesartan (10(-7) mol/L) + Lentiviral-ACE2 (MOI = 10) group ; (7) Lentiviral-ACE2 (MOI = 10) group. Ninety-six hours later, the proliferation of VSMCs was determined with CCK-8 Kit. AT1 receptor mRNA and protein expressions were detected with quantitative real-time PCR and Western blot, the signaling pathway of signal transducer and activator of transcription 3 (STAT3) was also detected.</p><p><b>RESULTS</b>ACE2 gene transfer significantly inhibited the VSMCs proliferation in the absence or presence of Ang II. AT1 receptor mRNA and protein expressions were also significantly downregulated in the absence or presence of Ang II. Similar to AT1 receptor mRNA and protein expression changes, STAT3 phosphorylation was also significantly inhibited by ACE2 overexpression.</p><p><b>CONCLUSION</b>Our results suggest that overexpression of ACE2 gene could inhibit the VSMCs proliferation by downregulating AT1 receptor expression and STAT3 phosphorylation. ACE2 could also directly inhibit AT1 receptor in cultured VSMCs.</p>