LAUSR

PAH is a pathophysiological state of abnormally elevated pulmonary arterial pressure caused by drugs, inflammation, toxins, viruses, hypoxia and other risk factors. We studied the therapeutic effect and target of TMP (tetramethylpyrazine) in the treatment of PAH and we speculated that dramatic changes in myocardin levels can significantly affect the progression of PAH. In vivo, the results showed that administration of TMP significantly prolonged the survival of PAH rats by reducing the proliferative lesions, RVSP, mPAP, and the Fulton index in the heart and lung of PAH rats. In vitro, TMP can regulate the levels of SM22-α, and myocardin as well as intracellular cytokines such as NO, TGF-β, and CTGF in a dose-dependent manner (25, 50, or 100 μM). Transfection of myocardin siRNA aggravated the proliferation of PSMCs, and the regulatory effect of TMP on α-SMA and OPN disappeared. The application of 10 nM ERα inhibitor MPP promoted the proliferation of PSMCs. But it does not affect the inhibition of TMP on PSMCs proliferation. Finally, we found that TMP promoted the nucleation of MRTF-A and combined it with myocardin. In conclusion, TMP can inhibit the transformation of PSMCs from the contractile phenotype to the proliferative phenotype by promoting the formation of the nuclear (MRTF-A/myocardin) transcription complex to treat PAH.