scholarly journals Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

2020 ◽  
Vol 21 (5) ◽  
pp. 1798 ◽  
Author(s):  
Gerrit M. Grosse ◽  
Edzard Schwedhelm ◽  
Hans Worthmann ◽  
Chi-un Choe
Keyword(s):  
Ischemic Stroke ◽  
Vascular Function ◽  
Cerebrovascular Diseases ◽  
Current Evidence ◽  
Clinical Implications ◽  
Pathophysiological Role ◽  
Health And Disease ◽  
Oxide Synthase ◽  
Derivatives Of

The amino acid L-arginine serves as substrate for the nitric oxide synthase which is crucial in vascular function and disease. Derivatives of arginine, such as asymmetric (ADMA) and symmetric dimethylarginine (SDMA), are regarded as markers of endothelial dysfunction and have been implicated in vascular disorders. While there is a variety of studies consolidating ADMA as biomarker of cerebrovascular risk, morbidity and mortality, SDMA is currently emerging as an interesting metabolite with distinct characteristics in ischemic stroke. In contrast to dimethylarginines, homoarginine is inversely associated with adverse events and mortality in cerebrovascular diseases and might constitute a modifiable protective risk factor. This review aims to provide an overview of the current evidence for the pathophysiological role of arginine derivatives in cerebrovascular ischemic diseases. We discuss the complex mechanisms of arginine metabolism in health and disease and its potential clinical implications in diverse aspects of ischemic stroke.

Role of the Adventitia in Pulmonary Vascular Remodeling

Physiology ◽  
2006 ◽  
Vol 21 (2) ◽  
pp. 134-145 ◽  
Author(s):  
Kurt R. Stenmark ◽  
Neil Davie ◽  
Maria Frid ◽  
Evgenia Gerasimovskaya ◽  
Mita Das
Keyword(s):  
Vascular Function ◽  
Vessel Wall ◽  
Vascular Wall ◽  
Current Evidence ◽  
Wall Function ◽  
Response To Stress ◽  
Health And Disease ◽  
Adventitial Fibroblast ◽  
Structural Behaviors

An increasing volume of experimental data indicates that the adventitial fibroblast, in both the pulmonary and systemic circulations, is a critical regulator of vascular wall function in health and disease. A rapidly emerging concept is that the vascular adventitia acts as biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. In response to stress or injury, resident adventitial cells can be activated and reprogrammed to exhibit different functional and structural behaviors. In fact, under certain conditions, the adventitial compartment may be considered the principal injury-sensing tissue of the vessel wall. In response to vascular stresses such as overdistension and hypoxia, the adventitial fibroblast is activated and undergoes phenotypic changes, which include proliferation, differentiation, upregulation of contractile and extracellular matrix proteins, and release of factors that directly affect medial smooth muscle cell tone and growth and that stimulate recruitment of inflammatory and progenitor cells to the vessel wall. Each of these changes in fibroblast phenotype modulates either directly or indirectly changes in overall vascular function and structure. The purpose of this review is to present the current evidence demonstrating that the adventitial fibroblast acts as a key regulator of pulmonary vascular function and structure from the “outside-in.”

scholarly journals The role of whey acidic protein four-disulfide-core proteins in respiratory health and disease

2017 ◽  
Vol 398 (4) ◽  
pp. 425-440 ◽  
Author(s):  
Donna M. Small ◽  
Declan F. Doherty ◽  
Caoifa M. Dougan ◽  
Sinéad Weldon ◽  
Clifford C. Taggart
Keyword(s):  
Protein Function ◽  
Respiratory Health ◽  
Whey Acidic Protein ◽  
Acidic Protein ◽  
Current Evidence ◽  
Core Proteins ◽  
Health And Disease ◽  
Low Molecular Weight Proteins ◽  
Potential Therapeutics

Abstract Members of the whey acidic protein (WAP) or WAP four-disulfide-core (WFDC) family of proteins are a relatively under-explored family of low molecular weight proteins. The two most prominent WFDC proteins, secretory leukocyte protease inhibitor (SLPI) and elafin (or the precursor, trappin-2), have been shown to possess multiple functions including anti-protease, anti-bacterial, anti-viral and anti-inflammatory properties. It is therefore of no surprise that both SLPI and elafin/trappin-2 have been developed as potential therapeutics. Given the abundance of SLPI and elafin/trappin-2 in the human lung, most work in the area of WFDC research has focused on the role of WFDC proteins in protecting the lung from proteolytic attack. In this review, we will outline the current evidence regarding the expanding role of WFDC protein function with a focus on WFDC activity in lung disease as well as emerging data regarding the function of some of the more recently described WFDC proteins.

Oxidative stress and endothelial dysfunction

2007 ◽  
Vol 27 (01) ◽  
pp. 5-12 ◽  
Author(s):  
G. Muller ◽  
C. Goettsch ◽  
H. Morawietz
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vessel Wall ◽  
Clinical Implications ◽  
Oxygen Species ◽  
Vascular Oxidative Stress ◽  
Arteries And Veins ◽  
Different Sources

SummaryThis review focuses on the role of vascular oxidative stress in the development and progression of endothelial dysfunction. We discuss different sources of oxidative stress in the vessel wall, oxidative stress and coagulation, the role of oxidative stress and vascular function in arteries and veins, the flow-dependent regulation of reactive oxygen species, the putative impact of oxidative stress on atherosclerosis, the interaction of angiotensin II, oxidative stress and endothelial dysfunction, and clinical implications.

scholarly journals miRNA Polymorphisms and Risk of Cardio-Cerebrovascular Diseases: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 20 (2) ◽  
pp. 293 ◽  
Author(s):  
Milad Bastami ◽  
Jalal Choupani ◽  
Zahra Saadatian ◽  
Sepideh Zununi Vahed ◽  
Yaser Mansoori ◽  
...  
Keyword(s):  
Systematic Review ◽  
Coronary Artery Disease ◽  
Congenital Heart Disease ◽  
Ischemic Stroke ◽  
Congenital Heart ◽  
Web Of Science ◽  
Meta Analysis ◽  
Cerebrovascular Diseases ◽  
Artery Disease

Recently extensive focus has been concentrated on the role of miRNAs in the initiation and progression of cardio-cerebrovascular diseases (CCDs) which constitute a range of conditions including cardiovascular diseases (CVDs, especially coronary artery disease (CAD)), congenital heart disease (CHD) and cerebrovascular diseases (CBVDs, especially the ischemic stroke (IS)). An increasing number of studies are evaluating the association between different miRNA polymorphisms and risk of CCDs, but results have been inconclusive. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and risk of CCDs. PubMed, Embase, Scopus, and Web of Science were queried to identify eligible articles. Odds ratios and 95% confidence intervals were used to assess the association of miRNA polymorphisms with CCD susceptibility. A total of 51 eligible articles evaluating the association of 31 miRNA polymorphisms were identified. Meta-analysis was performed for six miRNA polymorphisms. miR-146a rs2910164 (30 studies: 13,186 cases/14,497 controls), miR-149 rs2292832 (Nine studies: 4116 cases/3511 controls), miR-149 rs71428439 (Three studies: 1556 cases/1567 controls), miR-196a2 rs11614913 (20 studies: 10,144 cases/10,433 controls), miR-218 rs11134527 (Three studies: 2,322 cases/2,754 controls) were not associated with overall CCD. miR-499 rs3746444 was associated with CCD (20 studies: 9564 cases/8876 controls). In the subgroups, rs2910164 and rs3746444 were only associated with CVDs, especially CAD. In conclusion, the results support the existence of a role for miR-146a rs2910164 and miR-499 rs3746444 in determining susceptibility to CCDs, especially CAD.

scholarly journals Evidence for the Pathophysiological Role of Endogenous Methylarginines in Regulation of Endothelial NO Production and Vascular Function

2006 ◽  
Vol 282 (2) ◽  
pp. 879-887 ◽  
Author(s):  
Arturo J. Cardounel ◽  
Hongmei Cui ◽  
Alexandre Samouilov ◽  
Wesley Johnson ◽  
Patrick Kearns ◽  
...  
Keyword(s):  
Vascular Function ◽  
No Production ◽  
Pathophysiological Role

scholarly journals Evolving Concepts of Glycogen-Selective Autophagy

2021 ◽  
Author(s):  
Parisa Koutsifeli ◽  
Upasna Varma ◽  
Lorna Daniels ◽  
Marco Annandale ◽  
Xun Li ◽  
...  
Keyword(s):  
Degradation Pathway ◽  
Specific Protein ◽  
Current Evidence ◽  
Evolutionary Stage ◽  
Major Pathway ◽  
Selective Autophagy ◽  
Protein Partners ◽  
Health And Disease ◽  
Autophagy Pathway

Macro-autophagy is an essential cellular process involved in degradation of aberrant organelles and proteins. Initially proposed to be a ‘bulk’ degradation pathway, a more nuanced appreciation of selective autophagy pathways has emerged in recent years. The discovery of a glycogen-selective autophagy pathway (‘glycophagy’) has highlighted the importance of autophagy in regulating cellular metabolic homeostasis and identified a novel non-canonical major pathway of glycogen flux. The field of glycogen autophagy research is at an early evolutionary stage, but already it is clear that the implications of these discoveries are far-reaching and provide scope for multi-disciplinary investigations into the role of glycophagy in health and disease. With potential cognate protein partners identified, the opportunities for targeted intervention have become viable. Here we review the current evidence relating to specific protein mediators involved in glycophagy, and highlight areas of uncertainty that provide opportunity for further investigation.

scholarly journals Lipoprotein(a): An update on its role in human health and disease

2021 ◽  
Vol 12 (3) ◽  
pp. 92-102
Author(s):  
Amalia-Despoina Koutsogianni ◽  
Evangelos Liberopoulos ◽  
Alexandros D. Tselepis
Keyword(s):  
Cardiovascular Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Main Question ◽  
Lipoprotein A ◽  
The Past ◽  
Causal Risk Factor ◽  
Potential Clinical Benefit ◽  
Pathophysiological Role ◽  
Health And Disease

Over the past few years, there has been an undiminished interest on lipoprotein(a) [Lp(a)]. High Lp(a) levels have been proposed as an independent causal risk factor for atherosclerotic cardiovascular disease (CVD). The main question that remains to be answered, however, is the potential clinical benefit of Lp(a) reduction. This will contribute to the enrichment of our knowledge on the exact pathophysiological role of this lipoprotein. This narrative review aims to summarize currently available data on the structure, metabolism, and pathogenicity of Lp(a).

scholarly journals Potential role of perivascular adipose tissue in modulating atherosclerosis

2020 ◽  
Vol 134 (1) ◽  
pp. 3-13 ◽  
Author(s):  
Samah Ahmadieh ◽  
Ha Won Kim ◽  
Neal L. Weintraub
Keyword(s):  
Adipose Tissue ◽  
Vascular Function ◽  
Vessel Wall ◽  
Potential Role ◽  
Inflammatory Cells ◽  
Protective Role ◽  
Clinical Implications ◽  
Blood Vessel Wall ◽  
Perivascular Adipose Tissue

Abstract Perivascular adipose tissue (PVAT) directly juxtaposes the vascular adventitia and contains a distinct mixture of mature adipocytes, preadipocytes, stem cells, and inflammatory cells that communicate via adipocytokines and other signaling mediators with the nearby vessel wall to regulate vascular function. Cross-talk between perivascular adipocytes and the cells in the blood vessel wall is vital for normal vascular function and becomes perturbed in diseases such as atherosclerosis. Perivascular adipocytes surrounding coronary arteries may be primed to promote inflammation and angiogenesis, and PVAT phenotypic changes occurring in the setting of obesity, hyperlipidemia etc., are fundamentally important in determining a pathogenic versus protective role of PVAT in vascular disease. Recent discoveries have advanced our understanding of the role of perivascular adipocytes in modulating vascular function. However, their impact on cardiovascular disease (CVD), particularly in humans, is yet to be fully elucidated. This review will highlight the complex mechanisms whereby PVAT regulates atherosclerosis, with an emphasis on clinical implications of PVAT and emerging strategies for evaluation and treatment of CVD based on PVAT biology.

scholarly journals Diagnostic Utility and Pathogenic Role of Circulating MicroRNAs in Vasospastic Angina

2020 ◽  
Vol 9 (5) ◽  
pp. 1313
Author(s):  
Chan Soon Park ◽  
Inho Kim ◽  
Gyu Chul Oh ◽  
Jung-Kyu Han ◽  
Han-Mo Yang ◽  
...  
Keyword(s):  
Diagnostic Value ◽  
Vasospastic Angina ◽  
Circulating Microrna ◽  
Diagnostic Utility ◽  
Human Coronary Artery ◽  
Circulating Micrornas ◽  
Pathophysiological Role ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We investigated the diagnostic value and pathophysiological role of circulating microRNA (miR) in vasospastic angina (VA). We enrolled patients who underwent coronary angiography for chest pain to explore the miR’s diagnostic utility. In addition, we investigated the role of miRs in regulating endothelial nitric oxide synthase (eNOS) expression in human coronary artery endothelial cells (hCAECs). Among the 121 patients, 46 were diagnosed with VA (VA group), 26 with insignificant coronary lesions (ICL group), and 49 with atherothrombotic angina (AA group). The VA group showed a significantly higher expression of miR-17-5p, miR-92a-3p, and miR-126-3p than the ICL group. In contrast, miR-221-3p and miR-222-3p were upregulated in the AA group compared to the VA group, and all levels of miR-17-5p, miR-92a-3p, miR-126-3p, miR-145-5p, miR-221-3p, and miR-222-3p differed between the AA group and the ICL group. In the hCAECs, transfection with mimics (pre-miR) of miR-17-5p, miR-92a-3p, and miR-126-3p was associated with eNOS suppression. Additionally, transfection with inhibitors (anti-miR) of miR-92a-3p significantly rescued the eNOS suppression induced by lipopolysaccharide. In conclusion, the circulating miRs not only proved to have diagnostic utility, but also contributed to pathogenesis by eNOS regulation.

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