HIV-1 Tat Upregulates the Receptor for Advanced Glycation End Products and Superoxide Dismutase-2 in the Heart of Transgenic Mice.
HIV-1 Tat Upregulates the Receptor for Advanced Glycation End Products and Superoxide Dismutase-2 in the Heart of Transgenic Mice.
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DOI：
10.3390/v14102191
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发表时间：
2022-10-04
期刊：
影响因子：
--
通讯作者：
Paris JJ
中科院分区：
文献类型：
--
作者：
Qrareya AN;Wise NS;Hodges ER;Mahdi F;Stewart JA Jr;Paris JJ
心血管疾病（CVD）是HIV感染者（PLWH）常见的合并症。尽管其潜在机制尚不清楚，但病毒毒性HIV蛋白，如转录的反式激活因子（达特），可能有助于CVD发病机制。已经发现小鼠心肌中的达特表达诱导心脏功能障碍并增加内皮毒性的标志物。然而，达特在CVD发病机制中可能发挥的作用尚不清楚。使用AC 16人心肌细胞和条件性表达达特[达特（+）]或不表达[达特（-）]的成年雄性和雌性转基因小鼠评估达特影响心脏功能的能力。在AC 16心肌细胞中，达特增加细胞内钙。在达特（+）小鼠中，在心房和心室心脏组织中都检测到达特表达。与达特（-）对照组相比，达特（+）小鼠心室组织中晚期糖基化终产物受体和超氧化物歧化酶-2（SOD-2）的表达增加。SOD-1和α-平滑肌肌动蛋白无明显变化。尽管Tat介导的变化在细胞水平上，超声心动图测量没有变化。达特（+）小鼠的心室肥大细胞和胶原蛋白的比例更大;然而，多西环素暴露抵消了后者的影响。这些数据表明，达特暴露促进细胞变化，可以先于进展为CVD。
Cardiovascular disorder (CVD) is a common comorbidity in people living with HIV (PLWH). Although the underlying mechanisms are unknown, virotoxic HIV proteins, such as the trans-activator of transcription (Tat), likely contribute to CVD pathogenesis. Tat expression in mouse myocardium has been found to induce cardiac dysfunction and increase markers of endothelial toxicity. However, the role that Tat may play in the development of CVD pathogenesis is unclear. The capacity for Tat to impact cardiac function was assessed using AC16 human cardiomyocyte cells and adult male and female transgenic mice that conditionally expressed Tat [Tat(+)], or did not [Tat(−)]. In AC16 cardiomyocytes, Tat increased intracellular calcium. In Tat(+) mice, Tat expression was detected in both atrial and ventricular heart tissue. Tat(+) mice demonstrated an increased expression of the receptor for advanced glycation end products and superoxide dismutase-2 (SOD-2) in ventricular tissues compared to Tat(−) controls. No changes in SOD-1 or α-smooth muscle actin were observed. Despite Tat-mediated changes at the cellular level, no changes in echocardiographic measures were detected. Tat(+) mice had a greater proportion of ventricular mast cells and collagen; however, doxycycline exposure offset the latter effect. These data suggest that Tat exposure promotes cellular changes that can precede progression to CVD.
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影响因子：
14.9
作者：
Baldarelli RM;Smith CM;Finger JH;Hayamizu TF;McCright IJ;Xu J;Shaw DR;Beal JS;Blodgett O;Campbell J;Corbani LE;Frost PJ;Giannatto SC;Miers DB;Kadin JA;Richardson JE;Ringwald M
通讯作者：
Ringwald M
影响因子：
4.2
作者：
El Kamari V;Rodriguez K;Moser C;Currier JS;Kelesidis T;Stein JH;Brown TT;Howell SK;Beisswenger PJ;McComsey GA
通讯作者：
McComsey GA
影响因子：
3.1
作者：
Fukami, Kei;Yamagishi, Sho-ichi;Okuda, Seiya
通讯作者：
Okuda, Seiya
影响因子：
37.8
作者：
Feinstein MJ;Hsue PY;Benjamin LA;Bloomfield GS;Currier JS;Freiberg MS;Grinspoon SK;Levin J;Longenecker CT;Post WS
通讯作者：
Post WS
影响因子：
4.3
作者：
Chen Q;Wu Y;Yu Y;Wei J;Huang W
通讯作者：
Huang W