2208085J08) and Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (Grant No. 2021;12:18506. COVID-19 is also associated with liver injury. Luca Perico, Ariela Benigni, Giuseppe Remuzzi, Aldo Bonaventura, Alessandra Vecchi, Antonio Abbate, Zoya O. Serebrovska, Elisa Y. Chong, Lei Xi, Rafael Bellotti Azevedo, Bruna Gopp Botelho, Elizabeth Silaid Muxfeldt, Sarah Halawa, Soni S. Pullamsetti, Magdi H. Yacoub, Anglica Arcanjo, Jorgete Logullo, Alexandre Morrot, Toshifumi Matsuyama, Shawn P. Kubli, Tak W. Mak, Acta Pharmacologica Sinica Antiviral therapies and effective vaccination reduce viral load and could potentially offer endothelial protection in perivascular spaces [19]. These include tachycardia, shortness of breath, fatigue and post-exercise exhaustion. Katsoularis I, Fonseca-Rodrguez O, Farrington P, Lindmark K, Fors Connolly AM. However, the NPs from other coronaviruses such as Middle East respiratory syndrome coronavirus, SARS-CoV and H1N1 fail to cause endothelial activation, echoing the observation of endotheliitis, vasculopathy and coagulopathy in severe COVID-19 patients [45]. Here, we reviewed the potential mechanism of endothelial activation in COVID-19 by overviewing the most recent literature, with the aim to provide targeted therapies (Fig. 2020;26:101732. In addition to mtROS, other sources of ROS can also be possible, such as ROS derived from NADPH oxidase activation as well as eNOS uncoupling [85]. Eur Heart J. Virus-induced senescence is a driver and therapeutic target in COVID-19. Non-coding RNA. Article Kang X, Jin D, Jiang L, Zhang Y, Zhang Y, An X, et al. Cell Metab. Electron microscopy also show coronaviruses and vesicles containing virion particles in venous ECs [53] as well as LSECs from liver autopsy samples from COVID-19 patients [33]. Consistent with this notion, elevated level of C3a in severe COVID-19 patients induced the activation of CD16+ cytotoxic T cells which promotes endothelial injury and the release of monocyte chemoattractant proteins as well as neutrophil activation [96]. Circulation. Intriguingly, the main coronary arteries have no detectable expression of ACE2, suggesting the occurrence of COVID-19-induced endotheliitis in small vessel like capillaries; however, the culprit in the main coronaries are largely dependent on indirect mechanism arising from SARS-CoV-2 infection [47]. Mechanistically, patients with heart failure demonstrate increased ACE2 gene and protein expression, suggesting that if patients with heart failure were infected by the virus, they are more susceptible to severe COVID-19 and develop into a critically-ill conditions [28]. Int J Obes (2005). Respir Med. Further outstanding questions and research directions in the realm of endothelial dysfunction and COVID-19 include the following: The development of assays of assessing endothelial function in long COVID-19 patients and convalescents, such as brachial artery flow-mediated dilation (FMD) and arterial stiffness [carotid-femoral pulse wave velocity (cfPWV)]; This aspect is important considering the recent observation showing the decreased FMD in patients with COVID-19 stemming from expression of inflammatory cytokines/chemokines [176]; Cellular and animal models of evaluating endothelial dysfunction in COVID-19 to accelerate drug discovery; The therapeutic potential of specialized pro-resolving lipid mediators, such as resolvin D1, resolvin E1, aspirin-triggered resolvin D1 in resolving cytokine storm induced inflammatory responses can be pursued; The identification of alternative receptors for SARS-CoV-2 infection into different vascular beds beyond known ones (such as ACE2, AXL and L-SIGN) remain to be identified; Drug repurposing or high-throughput drug screening to identify new drugs targeting endothelial dysfunction in COVID-19; The role of epigenetic modification arising from DNA methylation and histone modification and long-lasting epigenetic memory effects caused by SARS-CoV2 infection in long COVID (postacute COVID-19 syndrome) remain to be evaluated [7]; Metabolic disturbance has been shown to be associated with the pathogenesis of COVID-19 [177]. Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial. 2021;15:70417. 7). Atypical presentation of Covid-19 in persons with spinal cord injury Biomedicines. Mental status changes and core temperature distinguish potentially fatal heat stroke from heat exhaustion. 2020;314:5862. 01 May 2023 01:18:34 2022;10:812. de Rooij L, Becker LM, Carmeliet P. A role for the vascular endothelium in post-acute COVID-19? J Intern Med. doi: 10.1097/MD.0000000000033345. Anakinra for severe forms of COVID-19: a cohort study. Poloni TE, Medici V, Moretti M, Vison SD, Cirrincione A, Carlos AF, et al. Chem-Biol Interact. Okada H, Yoshida S, Hara A, Ogura S, Tomita H. Vascular endothelial injury exacerbates coronavirus disease 2019: The role of endothelial glycocalyx protection. ACE2 agonism also blocks VEGF-A mediated pro-angiogenic signaling endothelial hyperpermeability. Also, CD209L/L-SIGN was identified as another receptor for mediating SARS-CoV-2 entry into human cells which can also interacts with ACE2 to facilitate SARS-CoV-2 entry [21]. In addition, nAChR activators may . Zhang L, Zhou L, Bao L, Liu J, Zhu H, Lv Q, et al. COVID-19 can manifest with myocardial injury (ischemic heart disease, arrhythmias and cardiomyopathies), arterial stiffness, liver injury and kidney injury [3]. Yang K, Holt M, Fan M, Lam V, Yang Y, Ha T, et al. A vicious cycle: in severe and critically Ill COVID-19 patients. Bookshelf SARS-CoV-2 spike protein impairs endothelial function via downregulation of ACE 2. Viruses. Physiological functions of the endothelium include fine control of vascular tone, tissue hemostasis, barrier integrity, inflammation, oxidative stress, vascular permeability, and structural and functional integrity [4]. Potje SR, Costa TJ, Fraga-Silva TFC, Martins RB, Benatti MN, Almado CEL, et al. However, conclusions need to be analyzed with caution due to small sample size [165]. Data from randomized controlled clinical trials are scarce. Recently, miR-98-5p was identified as a negative regulator of TMPRSS2 gene transcription in human lung and umbilical vein ECs [98]. Effectiveness and safety of traditional chinese medicine in treating COVID-19: clinical evidence from China. Cell Rep Med. Cardiovascular dysfunction in COVID-19: association between endothelial cell injury and lactate. The existence of cytokine storm could trigger vascular leakage, endothelial permeability in particular. FASEB J. However, blockade of TLR9 significantly mitigated SARS-CoV-2-induced IL-6 release and reversed SARS-CoV-2-induced eNOS downregulation. Would you like email updates of new search results? ACE2 is a key regulator of RAAS by catalyzing the production of Ang-(17) from AngII, and the Ang-(17) can act on MAS receptor to combat the harmful effects caused by activation of RAAS[87, 130].