Aydemir Basak G, Berenyiova Andrea, Cebova Martina, Henderson John D, Barta Andrej, Cacanyiova Sona
Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia.
Institute of Pathophysiology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia.
Pathophysiology. 2025 Jun 18;32(2):27. doi: 10.3390/pathophysiology32020027.
BACKGROUND/OBJECTIVES: Metabolic syndrome is one of the leading causes of mortality worldwide, with high-fat diet (HFD) intake being a significant driving force. Despite long-term research, new interventions are still being sought to improve cardiovascular disorders associated with metabolic syndrome.
To explore the therapeutic potential of a slow-releasing HS donor, we evaluated the effects of 3 weeks of treatment with GYY-4137 on systolic blood pressure (sBP), cardiac parameters, adiposity, selected plasma markers, and the vascular function of the thoracic aortas (TAs) and mesenteric arteries (MAs) isolated from male spontaneously hypertensive rats (SHRs) fed an HFD for 8 weeks.
HFD administration induced cardiac remodeling, increased adiposity, and decreased adrenergic contractility in both TAs and MAs. Moreover, although high-fat intake improved TAs relaxation, it decreased aortic protein expression of endothelial NO synthase and the involvement of NO in vasoactive responses of both TAs and MAs. In addition, protein expression of inducible NOS and tumor necrosis factor alpha (TNFα) in aortas was increased, as were plasma levels of chemerin, which has been proposed as a possible link among metabolic and vascular disorders and inflammation. Treatment with GYY-4137 reduced sBP, improved relaxation of the MAs, partially restored the contractility of the TAs, generally restored NO signaling, and decreased the protein expression of the inducible NOS and TNFα, as well as plasma chemerin levels.
A slow HS-releasing donor could partially ameliorate the metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the NO signaling restoration and suppression of inflammation.
背景/目的：代谢综合征是全球主要的死亡原因之一，高脂肪饮食（HFD）摄入是一个重要的驱动因素。尽管进行了长期研究，但仍在寻求新的干预措施来改善与代谢综合征相关的心血管疾病。
为了探索缓释硫化氢供体的治疗潜力，我们评估了用GYY-4137治疗3周对收缩压（sBP）、心脏参数、肥胖、选定的血浆标志物以及从喂食8周HFD的雄性自发性高血压大鼠（SHR）分离的胸主动脉（TA）和肠系膜动脉（MA）的血管功能的影响。
给予HFD可诱导心脏重塑、增加肥胖，并降低TA和MA中的肾上腺素能收缩力。此外，尽管高脂肪摄入改善了TA的舒张，但它降低了内皮型一氧化氮合酶的主动脉蛋白表达以及NO在TA和MA血管活性反应中的参与。此外，主动脉中诱导型一氧化氮合酶和肿瘤坏死因子α（TNFα）的蛋白表达增加，血浆chemerin水平也增加，chemerin被认为是代谢、血管疾病和炎症之间可能的联系。用GYY-4137治疗可降低sBP，改善MA的舒张，部分恢复TA的收缩力，总体上恢复NO信号，并降低诱导型一氧化氮合酶和TNFα的蛋白表达以及血浆chemerin水平。
缓释硫化氢供体可部分改善原发性高血压期间脂肪摄入增加引起的代谢变化，并触发与NO信号恢复和炎症抑制相关的有益血管活性作用。
