Effect of hydrogen sulfide on restenosis of peripheral arteries after angioplasty

Abstract

Abstract. Peripheral artery disease (PAD) may lead to a poor quality of life. Although percutaneous transluminal angioplasty (PTA) is widely used for the treatment of PAD, restenosis remains a major drawback. Hydrogen sulfide (H 2 S) plays potential roles in many physiological processes, such as vasodilatation and inhibition of smooth muscle cell proliferation. However, little is known regarding its role in arterial restenosis. In this study, we induced atherosclerotic-like lesions in rabbits, and we treated the rabbits with balloon angioplasty (BA) in a similar manner as PTA performed in the clinic. The rabbits were treated with sodium hydrosulfide (NaHS, a donor of H 2 S) or DL-propargylglycine (PPG, an inhibitor of H 2 S synthase). Treatment with NaHS significantly inhibited arterial restenosis following BA by reducing the intimal area and the intima/media ratio, while PPG treatment had a tendency to result in more severe restenosis. NaHS treatment significantly reduced smooth muscle cell (SMC) proliferation and elevated SMC apoptosis in the neointima. In contrast, PPG induced a significant increase in SMC proliferation. In conclusion, H 2 S attenuates the progression of neointimal hyperplasia and inhibits restenosis after BA. This discovery may lead to potential novel therapies, which can improve the prognosis of PAD patients.

Inhibition of endogenous hydrogen sulfide production exacerbates the inflammatory response during urine‑derived sepsis‑induced kidney injury

“…The results of the present study demonstrated that the expression levels of NF-κB, IL-6 and TGF-β1 in kidney tissues were significantly upregulated in the sepsis group when compared with the sham group at 48 h following surgery. Following treatment with PAG, endogenous H 2 S generation and kidney CSE activity were significantly reduced when compared with the untreated sepsis group, which is consistent with the results presented by Ma et al (38). In addition, PAG treatment significantly upregulated the expression of NF-κB and IL-6, and downregulated the expression of TGF-β1 in kidney tissues at 48 h following surgery when compared with the sepsis group.…”

Protective effect of a hydrogen sulfide donor on balloon injury-induced restenosis via the Nrf2/HIF-1α signaling pathway

“…It is well known that intimal hyperplasia induced by endothelial dysfunction and excessive VSMC proliferation is the central feature associated with the development of luminal stenosis diseases. During the treatment of these diseases, endovascular interventional therapies, including balloon catheter angioplasty, may induce exfoliation of endothelial cells, which triggers platelet activation and aggregation on vascular walls, leading to endothelial dysfunction (19). In response to these events, VSMCs switch to a proliferative phenotype.…”

“…In present study, a balloon injury model was used to investigate the molecular mechanisms underlying the anti-restenosis effects of H 2 S. Consistent with the hypothesis, the contents of H 2 S in the plasma and arterial tissues were increased in the balloon injury model following NaHS (a donor of H 2 S) treatment, whereas intimal hyperplasia was suppressed. Previously, using a rabbit model with atherosclerotic-like lesions, it was demonstrated that treatment with NaHS significantly inhibited arterial restenosis by reducing the intimal area and the intima/media ratio, accompanied by reduced SMC proliferation and elevated SMC apoptosis in the neointima (32). These results are similar to those obtained in the present study, and thereby indicate that H 2 S derived from exogenous NaHS is effective in treating experimentally induced vascular stenosis.…”

“…H 2 S is involved in a number of beneficial reactions in cardiovascular tissues, thereby regulating multiple physiological functions, including anti-oxidation, angiogenesis and vasodilation (17). According to the literature, H 2 S has cardioprotective effects via the inhibition of intimal hyperplasia after peripheral angioplasty (18,19) and antioxidative effects through the elimination of hydrogen peroxide (H 2 O 2 ) and superoxide anion, thereby suppressing myocardial ischemic injury (20). Nuclear factor-E2-related factor 2 (Nrf2), a transcription factor with a high sensitivity to oxidative stress, exerts antioxidative effects by binding to antioxidant response elements (AREs) in the nucleus and regulating the expression of downstream antioxidant genes, including heme oxygenase (HO)-1 (21).…”

Hydrogen Sulfide as a Potential Therapy for Heart Failure—Past, Present, and Future

“…Through both the investigation and success of these various H 2 S donors in relevant pre-clinical models such as HFrEF, we gain insight into the mechanisms of protective effects in pathological states seen in Figure 1. H 2 S therapy might be applied to similar states of not only pathological cardiac remodeling but a myriad of disease states involving, but not limited to, systemic inflammation, fibrosis, vascular diseases such as hypertension and peripheral artery disease [35][36][37][38], and overactive RAAS signaling.…”