Department of Pathology and Medical Biology - Division of Pathology, University of Groningen, University Medical Center Groningen. Hanzeplein 1 9700 RB Groningen, the Netherlands.
Department of Surgery - Division of Vascular Surgery, University of Groningen, University Medical Center Groningen. Hanzeplein 1 9700 RB Groningen, the Netherlands.
Sci Rep. 2016 Oct 6;6:34608. doi: 10.1038/srep34608.
Atherosclerotic plaques are classically divided into stable and vulnerable plaques. Vulnerable plaques are prone to rupture with a risk for infarction. High intraplaque microvessel density predisposes to plaque vulnerability. Hydrogen sulfide (HS) is a proangiogenic gasotransmitter which is endogenously produced by cystathionine γ-lyase (CSE), and is believed to have vasculoprotective effects. However, due to its proangiogenic effects, HS may result in pathological angiogenesis in atherosclerotic plaques, thereby increasing plaque vulnerability. The aim of this study was to determine CSE expression pattern in atherosclerotic plaques, and investigate whether CSE is involved in micro-angiogenesis in vitro. Endarterectomy plaques were studied for CSE expression, and the role of CSE in micro-angiogenesis was studied in vitro. CSE is expressed in plaques with similar levels in both stable and vulnerable plaques. CSE co-localized with von Willebrand Factor-positive microvessel endothelial cells and alpha-smooth-muscle actin-positive SMCs. In vitro, inhibition of CSE in HMEC-1 reduced tube formation, cell viability/proliferation, and migration which was restored after culture in the presence of HS donor GYY4137. CSE is expressed in intraplaque microvessels, and HS is a stimulator of micro-angiogenesis in vitro. Due to this pro-angiogenic effect, high levels of CSE in atherosclerotic plaques may be a potential risk for plaque vulnerability.
动脉粥样硬化斑块通常分为稳定斑块和易损斑块。易损斑块易破裂，有梗死的风险。斑块内微血管密度高易导致斑块易损。硫化氢（HS）是一种促血管生成的气体递质，由胱硫醚γ-裂解酶（CSE）内源性产生，具有血管保护作用。然而，由于其促血管生成作用，HS 可能导致动脉粥样硬化斑块中的病理性血管生成，从而增加斑块的易损性。本研究旨在确定动脉粥样硬化斑块中 CSE 的表达模式，并研究 CSE 是否参与体外微血管生成。对动脉内膜切除术斑块进行 CSE 表达研究，并在体外研究 CSE 在微血管生成中的作用。CSE 在稳定斑块和易损斑块中表达水平相似。CSE 与血管性血友病因子阳性微血管内皮细胞和α-平滑肌肌动蛋白阳性 SMC 共定位。在体外，HMEC-1 中 CSE 的抑制作用降低了管形成、细胞活力/增殖和迁移，而在 HS 供体 GYY4137 存在的情况下培养后，这些作用得到恢复。CSE 在斑块内微血管中表达，HS 是体外微血管生成的刺激物。由于这种促血管生成作用，动脉粥样硬化斑块中 CSE 的高水平可能是斑块易损性的潜在风险。
