scholarly journals Immune Mechanisms of Plaque Instability

2022 ◽  
Vol 8 ◽  
Author(s):  
Teresa Gerhardt ◽  
Arash Haghikia ◽  
Philip Stapmanns ◽  
David Manuel Leistner
Keyword(s):  
Cardiovascular Risk ◽  
Plaque Rupture ◽  
Global Perspective ◽  
Lipid Lowering ◽  
Plaque Vulnerability ◽  
Plaque Instability ◽  
Immune Mechanisms ◽  
Plaque Disruption ◽  
Therapeutic Concepts

Inflammation crucially drives atherosclerosis from disease initiation to the emergence of clinical complications. Targeting pivotal inflammatory pathways without compromising the host defense could compliment therapy with lipid-lowering agents, anti-hypertensive treatment, and lifestyle interventions to address the substantial residual cardiovascular risk that remains beyond classical risk factor control. Detailed understanding of the intricate immune mechanisms that propel plaque instability and disruption is indispensable for the development of novel therapeutic concepts. In this review, we provide an overview on the role of key immune cells in plaque inception and progression, and discuss recently identified maladaptive immune phenomena that contribute to plaque destabilization, including epigenetically programmed trained immunity in myeloid cells, pathogenic conversion of autoreactive regulatory T-cells and expansion of altered leukocytes due to clonal hematopoiesis. From a more global perspective, the article discusses how systemic crises such as acute mental stress or infection abruptly raise plaque vulnerability and summarizes recent advances in understanding the increased cardiovascular risk associated with COVID-19 disease. Stepping outside the box, we highlight the role of gut dysbiosis in atherosclerosis progression and plaque vulnerability. The emerging differential role of the immune system in plaque rupture and plaque erosion as well as the limitations of animal models in studying plaque disruption are reviewed.

Abstract P771: Monocyte-Chemoattractant Protein-1 Levels in Human Carotid Atherosclerosis Associate With Hallmarks of Plaque Vulnerability

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Marios K Georgakis ◽  
Sander W van der Laan ◽  
Yaw Asare ◽  
Joost M Mekke ◽  
Saskia Haitjema ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Intraplaque Hemorrhage ◽  
Vascular Risk ◽  
Plaque Vulnerability ◽  
Vascular Events ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Instability ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Background: Monocyte chemoattractant protein-1 (MCP-1) is a chemokine recruiting monocytes to the atherosclerotic plaque. Experimental, genetic, and epidemiological data support a key role of MCP-1 in atherosclerosis. Yet, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Methods: We measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy from the Athero-Express Biobank. We explored associations of plaque MCP-1 levels with histopathological features of plaque vulnerability, clinical plaque instability (symptomatic vs. asymptomatic plaque), molecular markers of plaque inflammation and remodeling, and with incident vascular events up to three years after plaque removal. Results: MCP-1 plaque levels were associated with individual histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage), as well as with a cumulative vulnerability index (range 0-5, beta: 0.42, 95%CI: 0.30-0.53, p=5.4x10 -13 ) independently of age, sex, and conventional vascular risk factors. Furthermore, MCP-1 levels were higher among patients with symptomatic, as compared to asymptomatic plaques (p=0.0001) and were associated with the levels of pro-inflammatory cytokines involved in leukocyte adhesion, as well as with matrix metalloproteinase activity in the plaque. In the follow-up analyses, MCP-1 levels were associated with a higher risk of peri-procedural events (up to 30 days after surgery). Conclusions: Our findings highlight a role of MCP-1 in human plaque vulnerability, the leading mechanism underlying vascular events like stroke and myocardial infarction. As such, they suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

Abstract 127: Induction of miR-21 Increases Fibrous Cap Stability in Vulnerable Atherosclerotic Lesions

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Hong Jin ◽  
Yuhuang Li ◽  
Alexandra Bäcklund ◽  
Albert Busch ◽  
Suzanne M Eken ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Cellular Proliferation ◽  
Plaque Rupture ◽  
Oxidized Ldl ◽  
Survival Rates ◽  
Experimental Models ◽  
Vascular Remodelling ◽  
Plaque Vulnerability ◽  
Plaque Instability ◽  
Asymptomatic Patients

The aim of the present study was to explore the role of miRNAs as potential regulators in patients with carotid artery stenosis and concordant vulnerable atherosclerotic plaques. A pre-determined miRNA-array of laser captured micro-dissected (LCM) tissue specimen from fibrous caps of 10 symptomatic patients (stroke or TIA within > 14 days and histo-morphologically identified ruptured lesion) compared to fibrous caps from 10 asymptomatic patients (stable lesions; high grade stenosis) discovered miR-21 as one of the two miRNAs (miRs-21 and -210) being substantially down-regulated in symptomatic patients. To functionally evaluate the contribution of miR-21 to plaque vulnerability, we created miR21 -/- / ApoE -/- mice on a C57BL/6 background. We explored the phenotype of these newly developed miR21 -/- /ApoE -/- mice in experimental models of vascular remodelling and plaque vulnerability. First, miR21 -/- mice revealed a complete lack of SMC proliferation in response to carotid ligation injury. In the second inducible plaque rupture model, using incomplete ligation of the common carotid artery with consecutive cuff placement proximal to the ligated region indicated that all miR21 -/- /ApoE -/- mice ( n =10) presented atherothombotic events and signs of severe plaque instability. The rupture rate in control miR21 +/+ /ApoE -/- mice was significantly lower at 56% ( n =9). In addition, miR21 -/- /ApoE -/- showed an increase in lesion area in the aortic root and substantially higher levels of macrophage infiltration in injured carotid arteries. Dynamic live cell imaging, using isolated aortic SMCs and peritoneal macrophages from miR21 -/- /ApoE -/- vs. miR2 +/+ /ApoE -/- mice displayed substantial lower cellular proliferation and survival rates (for SMCs), and distinct advanced inflammatory activity upon oxidized LDL (oxLDL) stimulation of macrophages. In the present study we identified miR-21 as a key modulator of pathologic processes in atherosclerosis-related vascular remodelling. Targeted, lesion-site specific overexpression of miR-21 could be a novel and powerful future strategy to stabilize vulnerable plaques by inducing pro-proliferative mechanisms in SMC-enriched fibrous caps.

scholarly journals Hydroxychloroquine: Looking into the Future

2017 ◽  
Vol 24 (4) ◽  
pp. 369-375 ◽  
Author(s):  
Saibal Chakravorty ◽  
Indranil Purkait ◽  
Anil Pareek ◽  
Avinash Talware
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Systemic Inflammation ◽  
Cardiovascular Effects ◽  
Lipid Lowering ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

AbstractHydroxychloroquine, an antimalarial agent has also been found to possess antidiabetic action. Onset of type-2 diabetes (T2DM) and cardiovascular disease is now considered to be the outcome of systemic inflammation. Many clinical trials are targeting systemic inflammation to reduce cardiovascular risk. Anti-inflammatory drugs with cardiovascular effects may be valuable therapeutic intervention to reduce massive cardiovascular risk in T2DM. In this review, antidiabetic action and potential cardioprotective role of hydroxychloroquine has been discussed. By virtue of its antidiabetic, lipid lowering, anti-platelet, anticoagulant and anti-inflammatory properties, hydroxychloroquine can be a key therapeutic alternative to manage patients with T2DM.

scholarly journals Seizure-Associated ST Elevation Myocardial Infarction in Absence of Plaque Rupture

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Haytham Mously ◽  
Mohammed Wazzan ◽  
Ahmed Z. Alkhathlan ◽  
Indiresha Iyer
Keyword(s):  
Myocardial Infarction ◽  
Rare Case ◽  
Seizure Activity ◽  
Plaque Rupture ◽  
St Elevation Myocardial Infarction ◽  
Coronary Syndrome ◽  
Plaque Disruption ◽  
St Elevation ◽  
The U.S

Acute coronary syndrome (ACS) is a very common cause of morbidity and mortality in the U.S. Here, we present a case of acute ST elevation myocardial infarction (STEMI) in the setting of seizure activity. In this rare case, we have data from optical coherence tomography (OCT) that showed no plaque disruption, showing the role of OCT in understanding the pathophysiology of STEMI and providing some ideas for the mechanism of this seizure-induced STEMI.

scholarly journals Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability

2020 ◽  
Author(s):  
Marios K Georgakis ◽  
Sander W. van der Laan ◽  
Yaw Asare ◽  
Joost M. Mekke ◽  
Saskia Haitjema ◽  
...  
Keyword(s):  
Intraplaque Hemorrhage ◽  
Vascular Risk ◽  
Plaque Vulnerability ◽  
Monocyte Chemoattractant Protein 1 ◽  
Plaque Instability ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Human Atherosclerosis ◽  
Plaque Inflammation

Monocyte chemoattractant protein-1 (MCP-1) recruits monocytes to the atherosclerotic plaque. While experimental, genetic, and observational data support a key role of MCP-1 in atherosclerosis, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Here, we measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy and explored associations with histopathological, molecular, and clinical features of plaque vulnerability. MCP-1 plaque levels were associated with histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage) as well as with molecular markers of plaque inflammation and matrix turnover, clinical plaque instability, and periprocedural stroke during plaque removal. Collectively, our findings highlight a role of MCP-1 in human plaque vulnerability and suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

scholarly journals The role of interleukin-18 in the development and progression of atherosclerosis

2020 ◽  
Vol 27 ◽  
Author(s):  
Afsane Bahrami ◽  
Thozhukat Sathyapalan ◽  
Amirhossein Sahebkar
Keyword(s):  
Plaque Rupture ◽  
Inflammatory Disorder ◽  
The Novel ◽  
Interleukin 18 ◽  
Therapeutic Approaches ◽  
Innate And Adaptive Immunity ◽  
Plaque Instability ◽  
Chronic Inflammatory Disorder ◽  
Preclinical And Clinical Studies

: Atherosclerosis (AS) as a chronic inflammatory disorder of the cardiovascular system, is one of the leading cause of ischemic heart disease, stroke and peripheral vascular disease. There is growing evidence on the role of innate and adaptive immunity in the pathogenesis of atherosclerosis. Interleukin-18 is one of the novel proinflammatory cytokines involved in the atherogenesis, atherosclerotic plaque instability and plaque rupture. In this review, we overview the findings of the preclinical and clinical studies about the role and mechanism of action of IL-18 in the pathogenesis of AS, which could offer novel prognostic and therapeutic approaches.

scholarly journals The role of obesity in carotid plaque instability: interaction with age, gender, and cardiovascular risk factors

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Valentina Rovella ◽  
Lucia Anemona ◽  
Marina Cardellini ◽  
Manuel Scimeca ◽  
Andrea Saggini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Carotid Plaque ◽  
Plaque Instability ◽  
Interaction With Age

MicroRNAs as sentinels and protagonists of carotid artery thromboembolism

2020 ◽  
Vol 134 (2) ◽  
pp. 169-192
Author(s):  
Sneha Raju ◽  
Jason E. Fish ◽  
Kathryn L. Howe
Keyword(s):  
Carotid Artery ◽  
Atherosclerotic Plaque ◽  
Carotid Plaque ◽  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Plaque Rupture ◽  
Cell Communication ◽  
Clinical Decision ◽  
Plaque Instability

Abstract Stroke is the leading cause of serious disability in the world and a large number of ischemic strokes are due to thromboembolism from unstable carotid artery atherosclerotic plaque. As it is difficult to predict plaque rupture and surgical treatment of asymptomatic disease carries a risk of stroke, carotid disease continues to present major challenges with regard to clinical decision-making and revascularization. There is therefore an imminent need to better understand the molecular mechanisms governing plaque instability and rupture, as this would allow for the development of biomarkers to identify at-risk asymptomatic carotid plaque prior to disease progression and stroke. Further, it would aid in creation of therapeutics to stabilize carotid plaque. MicroRNAs (miRNAs) have been implicated as key protagonists in various stages of atherosclerotic plaque initiation, development and rupture. Notably, they appear to play a crucial role in carotid artery thromboembolism. As the molecular pathways governing the role of miRNAs are being uncovered, we are learning that their involvement is complex, tissue- and stage-specific, and highly selective. Notably, miRNAs can be packaged and secreted in extracellular vesicles (EVs), where they participate in cell–cell communication. The measurement of EV-encapsulated miRNAs in the circulation may inform disease mechanisms occurring in the plaque itself, and therefore may serve as sentinels of unstable plaque as well as therapeutic targets.

Telmisartan in High Cardiovascular Risk Patients

2012 ◽  
Vol 8 (1) ◽  
pp. 10 ◽  
Author(s):  
Roland Asmar ◽  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Ace Inhibitors ◽  
Angiotensin Receptor Blockers ◽  
High Cardiovascular Risk ◽  
Raas Blockade ◽  
Risk Patients ◽  
Receptor Blockers ◽  
Current Guidelines

The worldwide morbidity and mortality burden of cardiovascular disease (CVD) is overwhelming and caused by increasing life expectancy and an epidemic of risk factors, including hypertension. Therapeutic options targeting different areas of the renin–angiotensin–aldosterone system (RAAS) to disrupt pathophysiological processes along the cardiovascular continuum are available. Angiotensin-converting enzyme (ACE) inhibitors are first-line treatments for CVD and angiotensin receptor blockers (ARBs) are suitable alternatives. Both ACE inhibitors and ARBs prevent CVD by lowering blood pressure (BP). Additionally, several studies have demonstrated that RAAS blockade can reduce cardiovascular risk beyond what might be expected from BP lowering alone. However, the ARBs are not all equally effective. Telmisartan is a long-lasting ARB that effectively controls BP over the full 24-hour period. Recently, the Ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET) study showed that telmisartan reduces cardiovascular events in high cardiovascular risk patients similarly to the gold standard ACE inhibitor ramipril beyond BP lowering alone, but with a better tolerability. Based on the results of the ONTARGET and Telmisartan randomized assessment study in ACE intolerant subjects with cardiovascular disease (TRANSCEND) studies, telmisartan is indicated for the reduction of cardiovascular morbidity. This article aims to review current guidelines for the management of CVD and consider key data from clinical trials and clinical practice evaluating the role of telmisartan in CVD.

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