More than Just a Monolayer: the Multifaceted Role of Endothelial Cells in the Pathophysiology of Atherosclerosis

Mußbacher, Marion; Schossleitner, Klaudia; Kral-Pointner, Julia B.; Salzmann, Manuel; Schrammel, Astrid; Schmid, Johannes A.

doi:10.1007/s11883-022-01023-9

Cited by 43 publications

(38 citation statements)

References 80 publications

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“…Raynaud’s phenomenon, or the onset of digital ulcers, may be considered a direct consequence of the imbalance between endothelium-derived relaxation and vasoconstrictive factors. Endothelial dysfunction is considered an early marker of atherosclerosis [ 37 ], so, therefore, we may assume that SSc could contribute per se to the development of accelerated atherosclerosis. Consistently, our findings ( Figure 1 and Figure 4 ) suggested that SSc could be involved in the pathogenetic chain of arterial stiffening.…”

Section: Discussionmentioning

confidence: 99%

The Impaired Elasticity of Large Arteries in Systemic Sclerosis Patients

Colaci

Zanoli

Gullo

et al. 2022

JCM

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(1) Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction and fibrosis of skin and visceral organs. In the last decade, attention has been focused on the macrovascular involvement of the disease. In particular, the observation of increased arterial stiffness represented an interesting aspect of the disease, as predictor of cardiovascular risk. (2) Methods: We recruited 60 SSc patients (52 ± 12 years old, 90% females) and 150 age/sex-matched healthy controls in order to evaluate both intima-media thickness of the right common carotid artery and arterial stiffness using the B-mode echography and the SphygmoCor system® tonometer. (3) Results: The carotid-femoral pulse wave velocity (PWV) was higher in SSc patients than in controls (8.6 ± 1.7 vs. 7.8 ± 1.5 m/s; p < 0.001), as was the carotid-radial PWV (7.8 ± 1.1 vs. 6.7 ± 1.4 m/s; p < 0.001). The intima-media thickness was higher in SSc than in controls (654 ± 108 vs. 602 ± 118 µm; p = 0.004). The other parameters measured at carotid (radial strain, Young’s modulus, compliance and distensibility) all indicated that arterial stiffness in tension was more pronounced in SSc. Of interest, the direct correlation between PWV and age corresponded closely in SSc. Moreover, a significant difference between SSc and controls as regards the carotid parameters was evident in younger subjects. (4) Conclusions: SSc patients showed an increased arterial stiffness compared to healthy controls. In particular, an SSc-related pathologic effect was suggested by the more pronounced increase in PWV with age and lower values of carotid elasticity in younger SSc patients than in age-matched controls.

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Section: Discussionmentioning

confidence: 99%

The Impaired Elasticity of Large Arteries in Systemic Sclerosis Patients

Colaci

Zanoli

Gullo

et al. 2022

JCM

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“…We do not maintain that these factors cause atherosclerosis but rather that they “prime the soil” in which lesions start to develop [ 20 ]. Endothelial cells are exposed to various degrees and types of shear stress, which have influence on their shape, intracellular signaling, and gene expression [ 21 ]. In the regular state, which is the quiescent state of the endothelium, nitric oxide (NO) is produced in order to bind to cysteine groups in NF-κB and the mitochondria, which inhibit cellular processes.…”

Section: Coronary Artery Disease and Atherosclerosismentioning

confidence: 99%

“…In the regular state, which is the quiescent state of the endothelium, nitric oxide (NO) is produced in order to bind to cysteine groups in NF-κB and the mitochondria, which inhibit cellular processes. Moreover, the endothelial layer is covered by a glycocalyx, which is layer of proteoglycans and extracellular matrix components, involved in transendothelial transport, e.g., of lipoproteins, which can be lost or reduced in inflammation due to plasminogen activator inhibitor [ 21 ]. In homeostasis, endothelial cells prevent platelet activation, blood clotting, and leukocyte adherence by secreting substances such as NO, prostacyclin, t-PA, and antithrombin III [ 21 ].…”

Section: Coronary Artery Disease and Atherosclerosismentioning

confidence: 99%

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

et al. 2022

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Cardiovascular diseases (CVDs) are disorders associated with the heart and circulatory system. Atherosclerosis is its major underlying cause. CVDs are chronic and can remain hidden for a long time. Moreover, CVDs are the leading cause of global morbidity and mortality, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of CVDs, focusing on coronary artery disease along with atherosclerosis as its major cause and arterial hypertension. We discuss the endothelium dysfunction, inflammatory factors, and oxidation associated with atherosclerosis. Mechanisms such as dysfunction of the endothelium and inflammation, which have been identified as critical pathways for development of coronary artery disease, have become easier to diagnose in recent years. Relatively recently, evidence has been found indicating that interactions of the molecular and cellular elements such as matrix metalloproteinases, elements of the immune system, and oxidative stress are involved in the pathophysiology of arterial hypertension. Many studies have revealed several important inflammatory and genetic risk factors associated with CVDs. However, further investigation is crucial to improve our knowledge of CVDs progression and, more importantly, accelerate basic research to improve our understanding of the mechanism of pathophysiology.

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“…), the ECs can sense these danger-associated molecular patterns (DAMP) and pathogen-associated molecular patterns (PAMP), thus transduce the innate immunity related signaling pathways to counteract the deleterious effects of these endogenous and exogenous danger molecules. Once this counter measure is defective, the harmful effects will continue to surge and immune disorders perpetuate in multiple tissues and organs ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…ECs can facilitate the phagocytosis of LDL and its oxidatively modified form-oxLDL, leading to endothelial dysfunction ( 11 ). LDL can also undergo transcytosis across EC membrane by receptors such as SR-BI and ALK ( 5 , 12 ). During the advanced stage of atherosclerosis, cardiovascular risk factors can promote endothelial apoptosis, leading to endothelial denudation, plaque erosion and thrombus formation ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

Endothelial Cells as a Key Cell Type for Innate Immunity: A Focused Review on RIG-I Signaling Pathway

Jin

Weng

2022

Front. Immunol.

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The vascular endothelium consists of a highly heterogeneous monolayer of endothelial cells (ECs) which are the primary target for bacterial and viral infections due to EC’s constant and close contact with the bloodstream. Emerging evidence has shown that ECs are a key cell type for innate immunity. Like macrophages, ECs serve as sentinels when sensing invading pathogens or microbial infection caused by viruses and bacteria. It remains elusive how ECs senses danger signals, transduce the signal and fulfil immune functions. Retinoic acid-inducible gene-I (RIG-I, gene name also known as DDX58) is an important member of RIG-I-like receptor (RLR) family that functions as an important pathogen recognition receptor (PRR) to execute immune surveillance and confer host antiviral response. Recent studies have demonstrated that virus infection, dsRNA, dsDNA, interferons, LPS, and 25-hydroxycholesterol (25-HC) can increase RIG-1 expression in ECs and propagate anti-viral response. Of translational significance, RIG-I activation can be inhibited by Panax notoginseng saponins, endogenous PPARγ ligand 15-PGJ2, tryptanthrin and 2-animopurine. Considering the pivotal role of inflammation and innate immunity in regulating endothelial dysfunction and atherosclerosis, here we provided a concise review of the role of RIG-I in endothelial cell function and highlight future direction to elucidate the potential role of RIG-I in regulating cardiovascular diseases as well as virus infectious disease, including COVID-19. Furthered understanding of RIG-I-mediated signaling pathways is important to control disorders associated with altered immunity and inflammation in ECs.

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More than Just a Monolayer: the Multifaceted Role of Endothelial Cells in the Pathophysiology of Atherosclerosis

Cited by 43 publications

References 80 publications

The Impaired Elasticity of Large Arteries in Systemic Sclerosis Patients

The Impaired Elasticity of Large Arteries in Systemic Sclerosis Patients

Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease

Endothelial Cells as a Key Cell Type for Innate Immunity: A Focused Review on RIG-I Signaling Pathway

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