School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.
Translational Genomics Laboratory, Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Gene. 2020 May 5;737:144479. doi: 10.1016/j.gene.2020.144479. Epub 2020 Feb 14.
Cardiac and renal dysfunction are often co-morbid pathologies leading to worsening prognosis resulting in difficulty in therapy of left ventricular hypertrophy (LVH). The aim of the current study was to determine the changes in expression of human ortholog genes of hypertension, vascular and cardiac remodeling and hypertensive nephropathy phenotypes under normal, disease and upon treatment with gasotransmitter including HS (hydrogen sulphide), NO (nitric oxide) and combined (HS + NO).
A total of 72 Wistar Kyoto rats (with equivalent male and female animals) were recruited in the present study where LVH rat models were treated with HS and NO individually as well as with both combined. Cardiac and renal physical indices were recorded and relative gene expression were quantified.
Both cardiac and renal physical indices were significantly modified with individual as well as combined HS + NO treatment in control and LVH rats. Expression analysis revealed, hypertension, vascular remodeling genes ACE, TNFα and IGF1, mRNAs to be significantly higher (P ≤ 0.05) in the myocardia and renal tissues of LVH rats, while individual and combined HS + NO treatment resulted in lowering the gene expression to normal/near to normal levels. The cardiac remodeling genes MYH7, TGFβ, SMAD4 and BRG1 expression were significantly up-regulated (P ≤ 0.05) in the myocardia of LVH where the combined HS + NO treatment resulted in normal/near to normal expression more effectively as compared to individual treatments. In addition individual as well as combined HS and NO treatment significantly decreased PKD1 expression in renal tissue, which was up-regulated in LVH rats (P ≤ 0.05).
The reduction in hemodynamic parameters and cardiac indices as well as alteration in gene expression on treatment of LVH rat model indicates important therapeutic potential of combined treatment with HS + NO gasotransmitters in hypertension and cardiac hypertrophy when present as co-morbidity with renal complications.
心脏和肾脏功能障碍常常是合并存在的病理情况，导致预后恶化，从而使左心室肥厚 (LVH) 的治疗变得困难。本研究的目的是确定在正常、疾病和用包括 HS（硫化氢）、NO（一氧化氮）和联合（HS+NO）在内的气体递质治疗下，高血压、血管和心脏重构以及高血压肾病表型的人类同源基因表达的变化。
本研究共招募了 72 只 Wistar Kyoto 大鼠（雄性和雌性动物数量相等），其中 LVH 大鼠模型分别接受 HS 和 NO 单独以及联合治疗。记录心脏和肾脏的物理指标，并定量相对基因表达。
在对照和 LVH 大鼠中，HS 和 NO 单独以及联合治疗均显著改变了心脏和肾脏的物理指标。表达分析显示，高血压、血管重构基因 ACE、TNFα 和 IGF1 的心肌和肾脏组织中的 mRNAs 表达显著升高（P≤0.05），而 HS 和 NO 单独和联合治疗使基因表达降低至正常/接近正常水平。心脏重构基因 MYH7、TGFβ、SMAD4 和 BRG1 的表达在 LVH 大鼠的心肌中显著上调（P≤0.05），联合 HS+NO 治疗比单独治疗更有效地使表达恢复正常/接近正常。此外，HS 和 NO 单独和联合治疗均显著降低了 LVH 大鼠肾脏组织中 PKD1 的表达（P≤0.05），PKD1 在 LVH 大鼠中上调。
LVH 大鼠模型治疗后血流动力学参数和心脏指数的降低以及基因表达的改变表明，HS+NO 气体递质联合治疗在高血压和心脏肥厚合并肾脏并发症时具有重要的治疗潜力。
