scholarly journals Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yarong Liu ◽  
Min Dai
Keyword(s):  
Gut Microbiota ◽  
Close Association ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
High Plasma ◽  
Chronic Inflammatory Disease ◽  
Biologically Active ◽  
Vascular Endothelial ◽  
Inflammatory Injury

Trimethylamine N-oxide (TMAO) is a biologically active molecule generated by the gut microbiota. Accumulating evidences have indicated a close association between high plasma TMAO levels and the risk of developing atherosclerosis (AS). AS is considered a chronic inflammatory disease initiated by vascular endothelial inflammatory injury. Both observational and experimental studies suggest that TMAO can cause endothelial inflammatory injury. However, a clear mechanistic link between TMAO and vascular inflammation of AS is not yet summarized. In this review, we discuss the association between TMAO and AS and focus on the potential role of TMAO in endothelial inflammatory injury. Finally, the utility of TMAO-targeted therapeutic strategies for the treatment of AS is also analyzed.

Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

2000 ◽  
Vol 80 (4) ◽  
pp. 1669-1699 ◽  
Author(s):  
Giuseppe Montrucchio ◽  
Giuseppe Alloatti ◽  
Giovanni Camussi
Keyword(s):  
Cardiovascular System ◽  
Cell Biology ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Experimental Studies ◽  
Platelet Activating Factor ◽  
Biologically Active ◽  
Endothelial Cell Migration

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

2007 George L. Duff Memorial Lecture—The Immune Response in Atherosclerosis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Göran K. Hansson
Keyword(s):  
Innate Immunity ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
Memorial Lecture ◽  
Immune Reactions ◽  
Specific Antigens ◽  
Atherosclerotic Process ◽  
Molecular Patterns ◽  
Lipoprotein Retention

Immune responses participate in every phase of atherosclerosis. Indeed, atherosclerosis can be viewed as an immune/inflammatory response to lipoprotein retention in the artery wall. There is increasing evidence that both adaptive and innate immunity tightly regulate the atherosclerotic process. Specific antigens and pathogen-like molecular patterns initiate the 2 aspects of immunity by ligating T- and B-cell receptors and pattern recognition receptors, respectively. Effector responses of vascular immune reactions include macrophage activation, cellular immunity, antibody formation, and vascular inflammation. Whereas experimental studies in gene-targeted models have identified major roles for innate immunity and Th1 responses in plaque initiation and progression, clinical, epidemiological and genetic studies suggest that plaque activation, rupture, and atherothrombosis also depend on immune reactions. This lecture will focus on the role of immune mechanisms in the formation and activation of atherosclerotic plaques.

scholarly journals Microbiota and Hypertension: Role of the Sympathetic Nervous System and the Immune System

2020 ◽  
Author(s):  
Iñaki Robles-Vera ◽  
Marta Toral ◽  
Juan Duarte
Keyword(s):  
T Cells ◽  
Nervous System ◽  
Immune System ◽  
Sympathetic Nervous System ◽  
Gut Microbiota ◽  
Current Knowledge ◽  
Vascular Inflammation ◽  
T Helper 17 ◽  
Sympathetic Nervous

Abstract There are numerous studies indicating a direct association between hypertension and gut microbiota in both animal models and humans. In this review, we focused on the imbalance in the gut microbiota composition relative to healthy state or homeostasis, termed dysbiosis, associated with hypertension and discuss the current knowledge regarding how microbiota regulates blood pressure (BP), involving the sympathetic nervous system and the immune system. The profile of ecological parameters and bacterial genera composition of gut dysbiosis in hypertension varies according to the experimental model of hypertension. Recent evidence supports that gut microbiota can protect or promote the development of hypertension by interacting with gut secondary lymph organs and altering T helper 17/regulatory T cells polarization, with subsequent changes in T cells infiltration in vascular tissues. Here, we also describe the bidirectional communication between the microbiome and the host via the sympathetic nervous system and its role in BP regulation. Dysbiosis in hypertension is mainly associated with reduced proportions of short-chain fatty acid-producing bacteria, mainly acetate- and butyrate-producing bacteria, and an increased enrichment of the genes for lipopolysaccharide biosynthesis and export, lending to moderate endotoxemia. The role of these metabolic and structural products in both immune and sympathetic system regulation and vascular inflammation was also analyzed. Overall, gut microbiota is now recognized as a well-established target to dietary interventions with prebiotics or probiotics to reduce BP.

scholarly journals Proinflammatory Role of Vascular Endothelial Growth Factor in the Pathogenesis of Rheumatoid Arthritis: Prospects for Therapeutic Intervention

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Seung-Ah Yoo ◽  
Seung-Ki Kwok ◽  
Wan-Uk Kim
Keyword(s):  
Rheumatoid Arthritis ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Current Knowledge ◽  
Chronic Inflammatory Disease ◽  
Vascular Endothelial ◽  
New Therapeutic Approaches ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Recent experimental and clinical studies have placed new emphasis on the role of angiogenesis in chronic inflammatory disease. Vascular endothelial growth factor (VEGF) and its receptors are the best characterized system in the regulation of rheumatoid arthritis (RA) by angiogenesis. Furthermore, in addition to its angiogenic role, VEGF can act as a direct proinflammatory mediator during the pathogenesis of RA, and protect rheumatoid synoviocytes from apoptosis, which contributes to synovial hyperplasia. Therefore, the developments of synovial inflammation, hyperplasia, and angiogenesis in the joints of RA patients seem to be regulated by a common cue, namely, VEGF. Agents that target VEGF, such as anti-VEGF antibody and aptamer, have yielded promising clinical data in patients with cancer or macular degeneration, and in RA patients, pharmacologic modulations targeting VEGF or its receptor may offer new therapeutic approaches. In this review, the authors integrate current knowledge of VEGF signaling and information on VEGF antagonists gleaned experimentally and place emphasis on the use of synthetic anti-VEGF hexapeptide to prevent VEGF interacting with its receptor.

scholarly journals Essential Role of Vascular Endothelial Growth Factor in Angiotensin II–Induced Vascular Inflammation and Remodeling

Hypertension ◽  
2004 ◽  
Vol 44 (3) ◽  
pp. 264-270 ◽  
Author(s):  
Qingwei Zhao ◽  
Minako Ishibashi ◽  
Ken-ichi Hiasa ◽  
Chunyan Tan ◽  
Akira Takeshita ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Essential Role ◽  
Vascular Inflammation ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Role of Peroxisome Proliferator-Activated Receptor-γin Vascular Inflammation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kousei Ohshima ◽  
Masaki Mogi ◽  
Masatsugu Horiuchi
Keyword(s):  
Immune Cells ◽  
Adipocyte Differentiation ◽  
Therapeutic Potential ◽  
Vascular Inflammation ◽  
Experimental Studies ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Important Regulator ◽  
Artery Disease

Vascular inflammation plays a crucial role in atherosclerosis, and its regulation is important to prevent cerebrovascular and coronary artery disease. The inflammatory process in atherogenesis involves a variety of immune cells including monocytes/macrophages, lymphocytes, dendritic cells, and neutrophils, which all express peroxisome proliferator-activated receptor-γ(PPAR-γ). PPAR-γis a nuclear receptor and transcription factor in the steroid superfamily and is known to be a key regulator of adipocyte differentiation. Increasing evidence from mainly experimental studies has demonstrated that PPAR-γactivation by endogenous and synthetic ligands is involved in lipid metabolism and anti-inflammatory activity. In addition, recent clinical studies have shown a beneficial effect of thiazolidinediones, synthetic PPAR-γligands, on cardiovascular disease beyond glycemic control. These results suggest that PPAR-γactivation is an important regulator in vascular inflammation and is expected to be a therapeutic target in the treatment of atherosclerotic complications. This paper reviews the recent findings of PPAR-γinvolvement in vascular inflammation and the therapeutic potential of regulating the immune system in atherosclerosis.

scholarly journals CURRENT EPIDEMIOLOGICAL KNOWLEDGE ABOUT THE ROLE OF FLAVONOIDS IN PROSTATE CARCINOGENESIS

2017 ◽  
Vol 39 (2) ◽  
pp. 98-105 ◽  
Author(s):  
K Sak
Keyword(s):  
Prostate Cancer ◽  
Dietary Habits ◽  
Experimental Studies ◽  
Prostate Cancer Risk ◽  
Health Benefit ◽  
Biologically Active ◽  
Western World ◽  
Plant Metabolites ◽  
Prostate Tumorigenesis

Numerous experimental studies have demonstrated anticancer action of polyphenolic plant metabolites. However, data about associations between dietary intake of plant-derived flavonoids and prostate cancer risk are still sparse and inconsistent. This minireview compiles the epidemiological findings published to date on the role of flavonoids in prostate tumorigenesis, discusses the reasons of inconsistencies and elicits the promising results for chemoprevention of this malignancy. Long-term consumption of high doses of soy isoflavones can be the reason of markedly lower clinically detectable prostate cancer incidence among Asian men compared to their counterparts in the Western world. The ability to metabolize daidzein to equol, the most biologically active isoflavone, by the certain intestinal bacteria also seems to contribute to this important health benefit. The increasing incidence rate of prostate cancer related to adoption of westernized lifestyle and dietary habits makes the issue of chemoprevention ever more important and directs the eyes to specific food components in the Eastern diet. If further large-scale epidemiological studies will confirm the protective effects of isoflavones against prostate cancer, this could provide an important way for prostate cancer prevention, as diet is a potentially modifiable factor in our behavioral pattern.

scholarly journals Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors

2011 ◽  
Vol 164 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Anniina Färkkilä ◽  
Mikko Anttonen ◽  
Jurate Pociuviene ◽  
Arto Leminen ◽  
Ralf Butzow ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Granulosa Cell ◽  
Biologically Active ◽  
Treatment Modalities ◽  
Vascular Endothelial ◽  
Granulosa Cell Tumors ◽  
Ovarian Granulosa Cell ◽  
Endothelial Growth Factor

ObjectiveOvarian granulosa cell tumors (GCTs) are hormonally active sex cord stromal tumors accounting for 3–5% of all ovarian cancers. These tumors are generally diagnosed at an early stage but there is a high risk of recurrence, associated with high mortality. Treatment of recurrent GCTs is difficult, and biologically targeted treatment modalities are lacking. GCTs are highly vascularized, and angiogenic factors most probably play a role in their pathology. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, but in GCTs, the role of VEGF and its receptors VEGFR-1 (FLT1) and VEGFR-2 (KDR) remains largely unknown. Our objective is to study the expression of VEGF and its receptors in human GCTs.MethodsWe analyzed GCTs from 106 patients for the expressions of VEGF and its receptors utilizing tumor tissue microarray, tumor mRNA, and patient serum samples.ResultsWe found that VEGF and its main biologically active receptor VEGFR-2 were highly expressed in primary and recurrent GCTs, when compared with normal granulosa-lutein cells. The expression of VEGF correlated positively to tumor microvessel density and to VEGFR-2 expression at the protein (P<0.05) and mRNA (P<0.05) levels. In contrast to VEGFR-2, the expression of VEGFR-1 was weak. Tumor VEGF protein expression was not prognostic for recurrence, however, we found high levels of circulating VEGF in the serum of patients with primary GCT.ConclusionsThe results suggest an important role of VEGF and VEGFR-2 in GCT pathology and support the possibility of applying novel VEGF- or VEGFR-2-targeted treatments to patients with GCT.

scholarly journals Interplay between Dietary Polyphenols and Oral and Gut Microbiota in the Development of Colorectal Cancer

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 625 ◽  
Author(s):  
Carolina Cueva ◽  
Mariana Silva ◽  
Iris Pinillos ◽  
Begoña Bartolomé ◽  
M. Victoria Moreno-Arribas
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Oral Bacteria ◽  
Intestinal Microbes ◽  
Therapeutic Implications ◽  
Dietary Polyphenols ◽  
Relevant Role

Colorectal cancer (CRC) is the third most diagnosed type of cancer worldwide. Dietary features play an important role in its development, and the involvement of human microbial communities in this pathology has also recently been recognized. Individuals with CRC display alterations in gut bacterial composition and a notably higher abundance of putative oral bacteria in colonic tumors. Many experimental studies and preclinical evidence propose that dietary polyphenols have a relevant role in CRC development and progression, mainly attributed to their immunomodulatory activities. Furthermore, polyphenols can modulate oral and gut microbiota, and in turn, intestinal microbes catabolize polyphenols to release metabolites that are often more active and better absorbed than the original phenolic compounds. The current study aimed to review and summarize current knowledge on the role of microbiota and the interactions between dietary polyphenols and microbiota in relation to CRC development. We have highlighted the mechanisms by which dietary polyphenols and/or their microbial metabolites exert their action on the pathogenesis and prevention of CRC as modulators of the composition and/or activity of oral and intestinal microbiota, including novel screening biomarkers and possible nutritional therapeutic implications.

Sign in / Sign up

Export Citation Format

Share Document