Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, CDMX, Mexico.
Instituto de Ciencias Aplicadas y Tecnología, Universidad Nacional Autónoma de México, CDMX, Mexico.
Exp Cell Res. 2019 Dec 15;385(2):111692. doi: 10.1016/j.yexcr.2019.111692. Epub 2019 Nov 2.
Arterial hypertension (HTN) can lead to serious organ damage. Several mechanisms have been implicated in the pathogenesis of HTN including constitutive activation of platelets, which increases the risk of aggregation and clot formation. We recently demonstrated the plasma membranes of platelets from patients with HTN exhibit modified structural and physicochemical properties; Raman and Fourier transform infrared by attenuated total reflectance (FTIR-ATR) spectroscopy also indicated lipid content and protein structure alterations. This study aimed to precisely quantify the constituents of the main structural phospholipids and cholesterol in the plasma membranes of platelets from patients with HTN and normotensive individuals. We also assessed the consequence of these alterations on platelet structure and function. Liquid chromatography coupled to triple quadrupole mass spectrometry revealed the plasma membranes of HTN platelets contained less cholesterol and phosphatidylcholine, more phosphatidylserine and phosphatidylethanolamine and had similar sphingosine contents. Atomic force microscopy revealed HTN platelets exhibited increased surface roughness and more pleats. Transmission electron microscopy revealed diminution of the internal membranous structures in HTN platelets. Our findings strongly suggest plasma membrane lipid content alterations-including cholesterol depletion-occur in HTN, and these alterations may induce morphological and physiological abnormalities that participate in the functional changes associated with hypertension.
动脉高血压(HTN)可导致严重的器官损伤。几种机制与 HTN 的发病机制有关,包括血小板的组成性激活,这增加了聚集和血栓形成的风险。我们最近证明了 HTN 患者的血小板的质膜具有修饰的结构和物理化学特性;拉曼和傅里叶变换衰减全反射(FTIR-ATR)光谱也表明脂质含量和蛋白质结构发生改变。本研究旨在精确定量 HTN 患者和血压正常个体的血小板质膜中主要结构磷脂和胆固醇的成分。我们还评估了这些改变对血小板结构和功能的影响。液质联用三重四极杆质谱法显示 HTN 血小板的质膜中胆固醇和磷脂酰胆碱减少,磷脂酰丝氨酸和磷脂酰乙醇胺增加,神经鞘氨醇含量相似。原子力显微镜显示 HTN 血小板的表面粗糙度增加,褶皱增多。透射电子显微镜显示 HTN 血小板的内部膜结构减少。我们的研究结果强烈表明,HTN 中存在质膜脂质含量的改变,包括胆固醇耗竭,这些改变可能诱导形态和生理异常,参与与高血压相关的功能变化。