Andriulė Inga, Pangonytė Dalia, Almanaitytė Mantė, Patamsytė Vaiva, Kuprytė Milda, Karčiauskas Dainius, Mubagwa Kanigula, Mačianskienė Regina
Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Department of Cardiac, Thoracic and Vascular Surgery, Hospital of Lithuanian University of Health Sciences Kauno Klinikos, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Sci Rep. 2021 Jul 29;11(1):15445. doi: 10.1038/s41598-021-94856-4.
The expression of the channels-enzymes TRPM6 and TRPM7 in the human heart remains poorly defined, and TRPM6 is generally considered not to be expressed in cardiomyocytes. We examined their expression at protein and mRNA levels using right atrial samples resected from patients (n = 72) with or without ischemic heart disease (IHD) and samples from all chamber walls of explanted human hearts (n = 9). TRPM6 and TRPM7 proteins were detected using immunofluorescence on isolated cardiomyocytes, ELISA on tissue homogenates, and immunostaining of cardiac tissue, whereas their mRNAs were detected by RT-qPCR. Both TRPM6 and TRPM7 were present in all chamber walls, with TRPM7 being more abundant. TRPM6 was co-expressed with TRPM7. The expression levels were dependent on cell incubation conditions (presence or absence of divalent cations, pH of the extracellular milieu, presence of TRP channel inhibitors 2-aminoethoxydiphenyl-borate and carvacrol). These drugs reduced TRPM7 immunofluorescence but increased that of TRPM6. TRPM6 and TRPM7 expression was increased in tissues from IHD patients. This is the first demonstration of the presence and co-expression of TRPM6 and TRPM7 in cardiomyocytes from all chamber walls of the human heart. The increased TRPM6 and TRPM7 expression in IHD suggests that the chanzymes are involved in the pathophysiology of the disease.
通道酶TRPM6和TRPM7在人心脏中的表达仍不清楚，并且一般认为TRPM6不在心肌细胞中表达。我们使用从患有或未患有缺血性心脏病（IHD）的患者（n = 72）切除的右心房样本以及来自移植的人心脏所有腔室壁的样本（n = 9），在蛋白质和mRNA水平上检测了它们的表达。使用分离的心肌细胞上的免疫荧光、组织匀浆上的ELISA以及心脏组织的免疫染色检测TRPM6和TRPM7蛋白，而通过RT-qPCR检测它们的mRNA。TRPM6和TRPM7在所有腔室壁中均存在，其中TRPM7更为丰富。TRPM6与TRPM7共表达。表达水平取决于细胞培养条件（二价阳离子的存在与否、细胞外环境的pH值、TRP通道抑制剂2-氨基乙氧基二苯硼酸和香芹酚的存在）。这些药物降低了TRPM7的免疫荧光，但增加了TRPM6的免疫荧光。IHD患者组织中TRPM6和TRPM7的表达增加。这是首次证明TRPM6和TRPM7在人心脏所有腔室壁的心肌细胞中存在并共表达。IHD中TRPM6和TRPM7表达的增加表明这些通道酶参与了该疾病的病理生理学过程。
