The relationship between estrogen-induced phenotypic transformation and proliferation of vascular smooth muscle and hypertensive intracerebral hemorrhage

Abstract

Background: To explore the effect of estrogen on human cerebral vascular smooth muscle cells (VSMCs) and to clarify the molecular mechanism of estrogen inhibition of VSMC proliferation, which could provide an important reference basis for the clinical treatment of hypertensive intracerebral hemorrhage. Method: Firstly, the effects of different concentrations of estradiol and estrogen receptor (ESR) blocker (tamoxifen) on the proliferation of human VSMCs and the expression of estrogen-related receptor gene (ESR: ESR1, ESR2, GPER), myocardin (MYOCD), serum reaction factor (SRF), and apoptosis gene caspase-3 were measured to discover the effect and mechanism of tamoxifen on the proliferation and apoptosis of VSMCs. Secondly, the effects of estradiol on human VSMCs treated with angiotensin II (Ang II) were observed by measuring the expression of vascular smooth muscle markers, α-smooth muscle actin (α-SMA), SM22α, FLN, MCP-1, and TLR4. Results: Estradiol inhibited the proliferation of VSMCs by upregulating the expression of ESR1, ESR2, and GPER and downregulating the expression of caspase-3, MYOCD, and SRF, thereby inhibiting the apoptosis of vascular smooth muscle. At the same time, tamoxifen had opposite effects. Angiotensin II decreased the expression of α-SMA and SM22α and promoted the expression of FLN, MCP-1, and TLR4 protein, while estrogen had the opposite effects.Conclusions: Estrogen suppresses apoptosis by inhibiting the proliferation of human VSMCs and preventing it from changing from contractile to synthetic. Estrogen can further prevents vascular damage and regulate peripheral inflammatory reaction, thereby producing a protective effect on cardiovascular and cerebrovascular.

MiR-22-3p Suppresses Vascular Remodeling and Oxidative Stress by Targeting CHD9 during the Development of Hypertension

“…1c). Among these 21 genes, MYC associated factor X [49], Sp1 transcription factor [50], cyclic adenosine monophosphate responsive element binding protein 1 [51], homeobox A4 [52], and estrogen receptor 1 [53] were previously reported to participate in the switch of ASMC phenotype. It was proposed that miR-22-3p might indirectly regulate CHD9 expression via these factors.…”

Blackcurrant (Ribes nigrum L.) Extract Exerts Potential Vasculoprotective Effects in Ovariectomized Rats, Including Prevention of Elastin Degradation and Pathological Vascular Remodeling

“…However, in the state of vascular injury or inflammation, VSMCs switch from the contractile phenotype to the synthetic phenotype, thereby playing an important role in vascular remodeling [ 39 , 40 , 41 ]. Estrogen can effectively prevent this switch [ 42 ]. As previously described, estrogen inhibits many processes, including VSMC migration and proliferation, via genomic and non-genomic mechanisms during vascular remodeling [ 3 , 35 , 36 ].…”

ILK play a key role in partial bladder outler obstruction (PBOO) by regulation TLR4/NF-κB(p65) pathway

“…On the other hand, it has been discovered by recent studies that TLR4/MyD88/NF-κB(p65) signal pathway could effectively regulate expression of SRF and Myocardin [20]. Olson Lab detected the most effective SRF coactivator by far-Myocardin which could initialize the phenotypic transformation procedure of smooth muscle cell (SMC) and activate the transcription of a series of SRF-regulated and codified cell scaffolding proteins and contraction-associated proteins so as to regulate the SMC phenotyping [20]. In this study, the findings suggest upon ILK overexpression, TGF-β1 stimulation and TLR4/MyD88/NF-κB(p65) activation, downstream SRF and Myocardin gene and proteins change in their expression.…”