Michael Tang

Introduction: Hypertension affects over 1 billion people and leads to numerous pathophysiologies and dysregulation of the cardiovascular, renal, and central nervous systems.¹ In addition, it is difficult to diagnose hypertension due to a lack of symptoms in the early stages, which leads to the commonly seen chronic diseases.^1,2,3 However, there has been recent research examining the association between hypertension and toll-like-receptors, especially TLR-4.^4,5 This article explores the relationship between endothelial dysfunction and immune cells with hypertension.  Methods: Review of major systems governing hypertension were analyzed for their effects on TLR-4. Specifically, the vascular smooth muscle cells in the corpora cavernosum vasculature of mice were studied with angiotensin II and TLR-4 antibody.⁶ Secondly, the neurological system and the cardiotonic steroids (CTS) like ouabain were assessed for increased proinflammatory products and components of the signaling cascade.^7,8 Lastly, the cardiovascular system and long non-coding RNAs (LncRNAs) were analyzed together.⁹ Results: Altogether, it can be shown that cellular damage leads to Damage-associated molecular patterns (DAMPs) and cause an upregulation of TLR-4.^4,5 Then, this leads to increased MyD88/TRIF/and other pathways, which activate downstream signaling via MKK, NF-κB and IRF3.^1,4,5 This, as well as angiotensin II, leads to increased NADPH oxidase, ROS accumulation, and results in pro-inflammatory mediators that control chronic low-grade inflammation.^3,5,7 Furthermore, LncRNAs CTBP1-AS2 was induced by a transcription factor SP1 and shown to be a novel regulator by interacting with an important RNA binding protein such as Fused in sarcoma (FUS) to stabilize TLR-4.⁹ Conclusion: Therapies can target CTS such as ouabain, LncRNAs and upstream/downstream mediators, or other parts of the described signaling complex. Yet, clinical trials have shown that these therapies must be tailored to different polymorphisms of TLR-4 and their susceptibility to chronic diseases.^10,11 Due to how many people hypertension affects and how deadly this disease is due to its difficult to detect, asymptomatic phase followed by an even more difficult to cure chronic phase, there begs a need to search for ways to treat this condition earlier and better, such as looking at TLR-4 inhibition in major organs.

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