Hydrogen sulfide has been suggested to play an essential role in atherogenesis. There is a paucity of information about the association between H2S and angiotensin converting enzyme 2 (ACE2), a novel homolog of ACE. Therefore, the aim of the study was to explore the role of H2S in atherosclerosis with respect to ACE2 both in vitro and in vivo. Here, a murine model of acutely disturbed flow-induced atherosclerosis by left common carotid artery (LCA) partial ligation was utilized. We found that carotid partial ligation in high-fat fed apoE−/− mice significantly inhibited endogenous H2S synthesis in LCA. Application of NaHS, an H2S donor considerably attenuated the severity of atherosclerosis with upregulating carotid expression of ACE2, thus converting pro-atherosclerotic angiotensin II (Ang II) to anti-atherosclerotic angiotensin 1-7 (Ang-(1-7)). The anti-atherosclerotic effect of NaHS was dramatically abolished by treatment with MLN-4760, an ACE2 inhibitor. In contrast, blockage of H2S formation by DL-propargylglycine exacerbated the burden of atherosclerotic plaques accompanied by inhibiting carotid expression of ACE2. At the cellular level, NaHS dose-dependently promoted the expression of ACE2 and conversion from Ang II to Ang-(1-7) in unstimulated or LPS-stimulated endothelial cells, thus exerting anti-inflammatory properties. The anti-inflammatory effect of NaHS was abrogated by pretreatment with DX600, a selective ACE2 inhibitor. In conclusion, these data provide direct evidences that endogenous H2S insufficiency exists in acute flow disturbance-induced atherosclerosis and that application of H2S may protect against atherosclerosis via upregulating ACE2 expression in endothelial cells.

Endothelial-to-mesenchymal transition (EndMT) serves an important role in the vascular remodeling of pulmonary arterial hypertension (PAH). However, little is known about the correlation between hydrogen sulfide (H2S), a protective gaseous mediator in PAH and the process of EndMT. Male Sprague-Dawley rats (10 weeks old) received a single dose of monocrotaline (MCT; i.p., 60 mg/kg) and were randomly treated with NaHS [an H2S donor; intraperitoneal (i.p.) 1 mg/kg/day], DL-propagylglycine (an inhibitor of H2S synthesis; PAG; i.p., 10 mg/kg/day) or saline, 7 days after MCT injection. Rats were sacrificed 21 days after MCT injection. A selection of human pulmonary artery endothelial cells (HPAECs) were pretreated with NaHS or saline and stimulated with transforming growth factor (TGF)-β1 (10 ng/ml), and the other HPAECs were transfected with a cystathionine γ-lyase (CSE, an H2S synthesizing enzyme) plasmid and subsequently stimulated with TGF-β1. NaHS was indicated to inhibit EndMT and PAH progression by inhibiting the induction of the nuclear factor (NF)-κB-Snail pathway. In contrast, the depletion of H2S formation by PAG exacerbated EndMT and PAH by activating NF-κB-Snail molecules. In HPAECs, NaHS dose-dependently inhibited TGF-β1-induced EndMT and the activation of the NF-κB-Snail pathway. Transfection with a CSE plasmid significantly repressed TGF-β1-induced expression of the mesenchymal marker and upregulated the expression of the endothelial marker, which was accompanied by the suppression of the NF-κB-Snail pathway. The inhibitory effect of CSE overexpression on TGF-β1-induced EndMT was significantly reversed by pretreatment with PAG. In conclusion, the current study provides novel information elucidating the beneficial effect of H2S on PAH through inhibiting the induction of the NF-κB-Snail pathway and the subsequent process of EndMT in pulmonary arteries.

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Purpose Adductor canal block (ACB) provides postoperative pain relief as effectively as femoral nerve block (FNB) does, and it preserves the strength of the quadriceps femoris. However, its effect on rehabilitation after arthroscopic partial meniscectomy has not been reported. The purpose of this study was to determine the effect of pre-operative ACB and FNB on the quality of rehabilitation after arthroscopic partial meniscectomy. Methods A total of 150 patients undergoing arthroscopic partial meniscectomy were randomly allocated to the FNB group (receiving 0.3% ropivacaine 30 ml at the thighroot-femoral nerve), the ACB group (receiving 0.3% ropivacaine 30 ml at mid-thigh adductor canal), or the control group. The primary outcome was the Hospital for Special Surgery (HSS) knee score on the 30th postoperative day. ResultsThe HSS knee score of the ACB group on the 30th day after the operation was significantly higher than those of the FNB and control groups (88.6 ± 5.3 vs. 85.3 ± 6.9 and 81.2 ± 5.9, respectively; P < 0.05). Both the ACB and FNB groups showed excellent rehabilitation, indicating similar rehabilitation quality for both treatments. Conclusion ACB is similar to FNB concerning the quality of rehabilitation and pain relief after arthroscopic partial meniscectomy, while ACB has little effect on the strength of the quadriceps femoris. Level of evidence I Trial registrataion This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INC-16008346).