Department of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia, U.S.A.
Graduate Program in Biological Sciences, Federal University of Goias, Goiânia, Brazil.
Clin Sci (Lond). 2020 Jan 31;134(2):303-313. doi: 10.1042/CS20190913.
Toll-like receptors (TLRs), such as TLR4 and 9, recognize pathogen-associated molecular pattern (PAMPs) and danger-associated molecular patterns (DAMPs) and are associated with increased blood pressure (BP). TLR3, residing in the endosomal compartment, is activated by viral double-stranded RNA (dsRNA) leading to activation of TIR receptor domain-containing adaptor inducing IFN-β (TRIF) dependent pathway. Besides foreign pathogens, the immune system responds to endogenous markers of cellular damage such as mitochondrial dsRNA (mtdsRNA). New evidence has shown a link between dsRNA and increased BP. Moreover, TLR3 activation during pregnancy was demonstrated to develop preeclampsia-like symptoms in both rats and mice. Hence, we hypothesize that the dsRNA derived from viral nucleic acids or cellular damage (mtdsRNA) will increase the inflammatory state through activation of TLR3, contributing to vascular dysfunction and increased BP. Therefore, inhibition of TLR3 could be a therapeutic target for the treatment of hypertension with potential improvement in vascular reactivity and consequently, a decrease in BP.
toll 样受体（TLRs），如 TLR4 和 9，识别病原体相关分子模式（PAMPs）和危险相关分子模式（DAMPs），与血压升高有关。TLR3 位于内体区室中，可被病毒双链 RNA（dsRNA）激活，导致 TIR 受体结构域包含衔接子诱导 IFN-β（TRIF）依赖性途径的激活。除了外来病原体，免疫系统还会对细胞损伤的内源性标志物（如线粒体双链 RNA（mtdsRNA））做出反应。新的证据表明 dsRNA 与血压升高之间存在联系。此外，研究表明，在大鼠和小鼠中，TLR3 在怀孕期间的激活会导致类似子痫前期的症状。因此，我们假设源自病毒核酸或细胞损伤（mtdsRNA）的 dsRNA 将通过激活 TLR3 增加炎症状态，导致血管功能障碍和血压升高。因此，TLR3 的抑制可能成为治疗高血压的治疗靶点，有可能改善血管反应性，从而降低血压。
