scholarly journals Vasculopathy in COVID-19

Blood ◽  
2022 ◽  
Author(s):  
Robert Flaumenhaft ◽  
Keiichi Enjyoji ◽  
Alec A Schmaier
Keyword(s):  
Cell Function ◽  
Vascular Complications ◽  
Respiratory Illness ◽  
Pulmonary Vasculature ◽  
Vascular Involvement ◽  
Barrier Dysfunction ◽  
Endothelial Cell Function ◽  
Systemic Involvement ◽  
New Information ◽  
Organ Systems

COVID-19 is a primary respiratory illness that is frequently complicated by systemic involvement of the vasculature. Vascular involvement leads to an array of complications ranging from thrombosis to pulmonary edema secondary to loss of barrier function. This review will address the vasculopathy of COVID-19 with a focus on the role of the endothelium in orchestrating the systemic response to SARS-CoV-2 infection. The endothelial receptor systems and molecular pathways activated in the setting of COVID-19 and the consequences of these inflammatory and prothrombotic changes on endothelial cell function will be discussed. The sequelae of COVID-19 vascular involvement at the level of organ systems will also be addressed, with an emphasis on the pulmonary vasculature, but with consideration of effects on other vascular beds. The dramatic changes in endothelial phenotypes associated with COVID-19 has enabled the identification of biomarkers that could help guide therapy and predict outcomes. Knowledge of vascular pathogenesis in COVID-19 has also informed therapeutic approaches that may control its systemic sequelae. Since our understanding of vascular response in COVID-19 continues to evolve, we will consider areas of controversy, such as the extent to which SARS-CoV-2 directly infects endothelium and the degree to which vascular responses to SARS-CoV-2 are unique or common to those of other viruses capable of causing severe respiratory disease. This conceptual framework describing how SARS-CoV-2 infection affects endothelial inflammation, prothrombotic transformation, and barrier dysfunction will provide a context for interpreting new information as it arises addressing the vascular complications of COVID-19.

scholarly journals Targeting QKI-7 in vivo restores endothelial cell function in diabetes

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Chunbo Yang ◽  
Magdalini Eleftheriadou ◽  
Sophia Kelaini ◽  
Thomas Morrison ◽  
Marta Vilà González ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Vascular Endothelial Cell ◽  
Vascular Complications ◽  
Limb Ischemia ◽  
Limb Amputation ◽  
Diabetic Patients ◽  
Ips Cell ◽  
Endothelial Cell Function

Abstract Vascular endothelial cell (EC) dysfunction plays a key role in diabetic complications. This study discovers significant upregulation of Quaking-7 (QKI-7) in iPS cell-derived ECs when exposed to hyperglycemia, and in human iPS-ECs from diabetic patients. QKI-7 is also highly expressed in human coronary arterial ECs from diabetic donors, and on blood vessels from diabetic critical limb ischemia patients undergoing a lower-limb amputation. QKI-7 expression is tightly controlled by RNA splicing factors CUG-BP and hnRNPM through direct binding. QKI-7 upregulation is correlated with disrupted cell barrier, compromised angiogenesis and enhanced monocyte adhesion. RNA immunoprecipitation (RIP) and mRNA-decay assays reveal that QKI-7 binds and promotes mRNA degradation of downstream targets CD144, Neuroligin 1 (NLGN1), and TNF-α-stimulated gene/protein 6 (TSG-6). When hindlimb ischemia is induced in diabetic mice and QKI-7 is knocked-down in vivo in ECs, reperfusion and blood flow recovery are markedly promoted. Manipulation of QKI-7 represents a promising strategy for the treatment of diabetic vascular complications.

Urokinase mediates fibrinolysis in the pulmonary microvasculature

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1820-1826 ◽  
Author(s):  
Khalil Bdeir ◽  
Juan-Carlos Murciano ◽  
John Tomaszewski ◽  
Lauren Koniaris ◽  
Jose Martinez ◽  
...  
Keyword(s):  
Physical Properties ◽  
Plasminogen Activator ◽  
Cell Function ◽  
Tissue Type ◽  
Pulmonary Vasculature ◽  
Clot Lysis ◽  
Single Chain ◽  
Endothelial Cell Function ◽  
Type Plasminogen Activator ◽  
Endogenous Fibrinolysis

The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in fibrinolysis remains unsettled. The contribution of uPA may depend on the vascular location, the physical properties of the clot, and its impact on tissue function. To study the contribution of urokinase within the pulmonary microvasculature, a model of pulmonary microembolism in the mouse was developed. Iodine 125 (125I)–labeled fibrin microparticles injected intravenously through the tail vein lodged preferentially in the lung, distributing homogeneously throughout the lobes. Clearance of125I-microemboli in wild type mice was rapid and essentially complete by 5 hours. In contrast, uPA−/− and tissue-type plasminogen activator tPA−/− mice, but not uPAR−/− mice, showed a marked impairment in pulmonary fibrinolysis throughout the experimental period. The phenotype in the uPA−/− mouse was rescued completely by infusion of single chain uPA (scuPA). The increment in clot lysis was 4-fold greater in uPA−/− mice infused with the same concentration of scuPA complexed with soluble recombinant uPAR. These data indicate that uPA contributes to endogenous fibrinolysis in the pulmonary vasculature to the same extent as tPA in this model system. Binding of scuPA to its receptor promotes fibrinolytic activity in vivo as well as in vitro. The physical properties of fibrin clots, including size, age, and cellular composition, as well as heterogeneity in endothelial cell function, may modify the participation of uPA in endogenous fibrinolysis.

The role of the vascular endothelium in arenavirus haemorrhagic fevers

2009 ◽  
Vol 102 (12) ◽  
pp. 1024-1029 ◽  
Author(s):  
Stefan Kunz
Keyword(s):  
Vascular Endothelium ◽  
Cell Function ◽  
Experimental Studies ◽  
Lassa Fever ◽  
Vascular Involvement ◽  
Lassa Virus ◽  
South American ◽  
The South ◽  
Endothelial Cell Function

SummaryViral haemorrhagic fevers (VHF) caused by arenaviruses are among the most devastating emerging human diseases.The most important pathogen among the arenaviruses is Lassa virus (LASV), the causative agent of Lassa fever that is endemic to West Africa. On the South American continent, the New World arenavirus Junin virus (JUNV), Machupo (MACV), Guanarito (GTOV), and Sabia virus (SABV) have emerged as causative agents of severe VHFs. Clinical and experimental studies on arenavirus VHF have revealed a crucial role of the endothelium in their pathogenesis. However, in contrast to other VHFs, haemorrhages are not a salient feature of Lassa fever and fatal cases do not show overt destruction of vascular tissue.The functional alteration of the vascular endothelium that precede shock and death in fatal Lassa fever may be due to more subtle direct or indirect effects of the virus on endothelial cells. Haemorrhagic disease manifestations and vascular involvement are more pronounced in the VHF caused by the South American haemorrhagic fever viruses. Recent studies on JUNV revealed perturbation of specific endothelial cell function, including expression of cell adhesion molecules, coagulation factors, and vasoactive mediators as a consequence of productive viral infection.These studies provided first possible links to some of the vascular abnormalities observed in patients; however, their relevance in vivo remains to be investigated.

Urokinase mediates fibrinolysis in the pulmonary microvasculature

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1820-1826 ◽  
Author(s):  
Khalil Bdeir ◽  
Juan-Carlos Murciano ◽  
John Tomaszewski ◽  
Lauren Koniaris ◽  
Jose Martinez ◽  
...  
Keyword(s):  
Physical Properties ◽  
Plasminogen Activator ◽  
Cell Function ◽  
Tissue Type ◽  
Pulmonary Vasculature ◽  
Clot Lysis ◽  
Single Chain ◽  
Endothelial Cell Function ◽  
Type Plasminogen Activator ◽  
Endogenous Fibrinolysis

Abstract The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in fibrinolysis remains unsettled. The contribution of uPA may depend on the vascular location, the physical properties of the clot, and its impact on tissue function. To study the contribution of urokinase within the pulmonary microvasculature, a model of pulmonary microembolism in the mouse was developed. Iodine 125 (125I)–labeled fibrin microparticles injected intravenously through the tail vein lodged preferentially in the lung, distributing homogeneously throughout the lobes. Clearance of125I-microemboli in wild type mice was rapid and essentially complete by 5 hours. In contrast, uPA−/− and tissue-type plasminogen activator tPA−/− mice, but not uPAR−/− mice, showed a marked impairment in pulmonary fibrinolysis throughout the experimental period. The phenotype in the uPA−/− mouse was rescued completely by infusion of single chain uPA (scuPA). The increment in clot lysis was 4-fold greater in uPA−/− mice infused with the same concentration of scuPA complexed with soluble recombinant uPAR. These data indicate that uPA contributes to endogenous fibrinolysis in the pulmonary vasculature to the same extent as tPA in this model system. Binding of scuPA to its receptor promotes fibrinolytic activity in vivo as well as in vitro. The physical properties of fibrin clots, including size, age, and cellular composition, as well as heterogeneity in endothelial cell function, may modify the participation of uPA in endogenous fibrinolysis.

Do DPP-4 inhibitors improve endothelial cell function?

2017 ◽  
Vol 01 (01) ◽  
Author(s):  
Hiroshi Nomoto ◽  
Hideaki Miyoshi ◽  
Akinobu Nakamura ◽  
Tatsuya Atsumi ◽  
Naoki Manda ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Endothelial Cell Function

Estrogen Restores Endothelial Cell Function in an Experimental Model of Vascular Injury

Circulation ◽  
1997 ◽  
Vol 96 (5) ◽  
pp. 1624-1630 ◽  
Author(s):  
C. Roger White ◽  
Jonathan Shelton ◽  
Shi-Juan Chen ◽  
Victor Darley-Usmar ◽  
Leslie Allen ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Experimental Model ◽  
Vascular Injury ◽  
Cell Function ◽  
Endothelial Cell Function

scholarly journals CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation

2009 ◽  
Vol 296 (3) ◽  
pp. H689-H697 ◽  
Author(s):  
Karen Y. Stokes ◽  
LeShanna Calahan ◽  
Candiss M. Hamric ◽  
Janice M. Russell ◽  
D. Neil Granger
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
T Cell ◽  
Blood Cell ◽  
Cell Function ◽  
Inflammatory Responses ◽  
Microvascular Dysfunction ◽  
Cd40 Ligand ◽  
Scid Mice ◽  
Endothelial Cell Function

Hypercholesterolemia is associated with phenotypic changes in endothelial cell function that lead to a proinflammatory and prothrombogenic state in different segments of the microvasculature. CD40 ligand (CD40L) and its receptor CD40 are ubiquitously expressed and mediate inflammatory responses and platelet activation. The objective of this study was to determine whether CD40/CD40L, in particular T-cell CD40L, contributes to microvascular dysfunction induced by hypercholesterolemia. Intravital microscopy was used to quantify blood cell adhesion in cremasteric postcapillary venules, endothelium-dependent vasodilation responses in arterioles, and microvascular oxidative stress in wild-type (WT) C57BL/6, CD40-deficient (−/−), CD40L−/−, or severe combined immune deficient (SCID) mice placed on a normal (ND) or high-cholesterol (HC) diet for 2 wk. WT-HC mice exhibited an exaggerated leukocyte and platelet recruitment in venules and impaired vasodilation responses in arterioles compared with ND counterparts. A deficiency of CD40, CD40L, or lymphocytes attenuated these responses to HC. The HC phenotype was rescued in CD40L−/− and SCID mice by a transfer of WT T cells. Bone marrow chimeras revealed roles for both vascular- and blood cell-derived CD40 and CD40L in the HC-induced vascular responses. Hypercholesterolemia induced an oxidative stress in both arterioles and venules of WT mice, which was abrogated by either CD40 or CD40L deficiency. The transfer of WT T cells into CD40L−/− mice restored the oxidative stress. These results implicate CD40/CD40L interactions between circulating cells and the vascular wall in both the arteriolar and venular dysfunction elicited by hypercholesterolemia and identify T-cell-associated CD40L as a key mediator of these responses.

scholarly journals Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

2021 ◽  
Vol 22 (11) ◽  
pp. 5635
Author(s):  
Katharina Urschel ◽  
Miyuki Tauchi ◽  
Stephan Achenbach ◽  
Barbara Dietel
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Cell Function ◽  
Computational Techniques ◽  
Apical Surface ◽  
Cardiovascular Research ◽  
Endothelial Cell Function ◽  
Wall Shear

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.

scholarly journals AB0608 CARDIAC VESSELS CALCIFICATION IN A COHORT OF SYSTEMIC SCLEROSIS PATIENTS: POSSIBLE ROLE IN VASCULOPATHY AND HEART ABNORMALITIES.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1600.2-1600
Author(s):  
S. Sciacca ◽  
C. Rotondo ◽  
A. Corrado ◽  
L. Giardullo ◽  
S. Stefania ◽  
...  
Keyword(s):  
Uric Acid ◽  
Systemic Sclerosis ◽  
Disease Duration ◽  
Vascular Complications ◽  
Hypovitaminosis D ◽  
Older Age ◽  
Vascular Involvement ◽  
Cvd Risk ◽  
1 John ◽  
The Impact

Background:Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Myocardial calcifications have been related with cardiovascular diseases (CVD) such as focal wall motion abnormalities and arrhythmias. The impact of vascular calcifications is under investigation in order to define the risk of cardiovascular events. The relationship between cardiac calcification and systemic sclerosis (SSc) has not been investigated.Objectives:The aim of the study is to evaluate the frequency of different patterns of cardiac calcification in SSc patients, and to correlate them to other CVD risk factors.Methods:We analyzed thoracic-CT scanners of 35 SSc patients (88% female, aged 47,8 ys ±12,9, disease duration 12,8 ys ±9) to determine the location and extension of vascular and cardiac calcification. All recruited patients fulfilled the 2013 ACR-EULAR classification criteria for SSc. No one patients had renal failure, cardiomyopathy, myocarditis, history of cardiac surgery or radiotherapy.Results:We found myocardial vessels calcifications (MCv) in 37% SSc patients, aortic wall calcifications (ACw)in 60% SSc patients, cardiac valve calcifications (VC) in 28% SSc patient and heart wall calcifications (HCw) in 20%.The SSc patients with almost one calcification had older age (65±9,8 ys vs 50±8,8 ys; p=0,0001) and higher values of circulating NTproBNP (336,9±351,9 vs 144,2±107,8; p=0,04) compared to those without.In particular, the SSc patients with MCv had and uric acid (5,3 ±1,5 vs 4,1 ±1,3; p=0,05), higher rate of PAH (25% vs 0%; p=0,037), arrhythmia (38,5% vs 9%; p=0,036) and higher prevalence of CENP-B antibodies(46% vs 4%; p=0,01) compared to patients without MCv.Patients with HCw had lower C reactive protein (0,16 ±0,10 vs 0,7±0,7; p=0,008) compared to those without HCw. No differences in the rate of heart and vascular complications of SSc were observed.The SSc patients with ACw had higher frequency of arrhythmia (33% vs 0%; p=0,016) and longer disease duration (15,5 y ±9,9 vs 8,8 ±5,8; p=0,03).The SSc patients with VC had higher rate of PAH (33%vs0%; p=0,003) and uric acid (6±0,5vs3,8±1,2 p=0,0001).Regression analysis excluded any association with gender, BMI, systemic arterial hypertension, steroid therapy, hypovitaminosis D or smoke habit. No cardiovascular event was recorded in one year of observation.Conclusion:All patterns of calcifications may be related mostly with the older age. Myocardial vessels calcifications have been found in a high percentage of SSc patients and in particular in those with PAH and positive for anti CENP-B. Furthermore, myocardial vessels calcifications could be associated to the higher occurrence of arrhythmia. More studied are needed to assess the importance of vascular calcification as a part of the vascular involvement in SSc.References:[1]John W. Nance Jr. MD. Myocardial calcifications: Pathophysiology, etiologies, differential diagnoses, and imaging findings. Journal of Cardiovascular Computed Tomography 9 (2015) 58 e 67.[2]Pagkopoulou E, Poutakidou M. Cardiovascular risk in systemic sclerosis: Micro- and Macro-vascular involvement. Indian J Rheumatol 2017;12, Suppl S1:211-7[3]Plastiras SC, Toumanidis ST. Systemic sclerosis: the heart of the matter. Hellenic J Cardiol. 2012;53(4):287–300.Disclosure of Interests:None declared

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