Glucocorticoids are active players and therapeutic targets in atherosclerotic cardiovascular disease

With the incidence and impact of atherosclerotic cardiovascular disease and its clinical manifestations still rising, therapeutic options that target the causal mechanisms of this disorder are highly desired. Since the CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) has demonstrated that lowering inflammation can be beneficial, focusing on mechanisms underlying inflammation, for example, leukocyte recruitment, is feasible. Being key orchestrators of leukocyte trafficking, chemokines have not lost their attractiveness as therapeutic targets, despite the difficult road to drug approval thus far. Still, innovative therapeutic approaches are being developed, paving the road towards the first chemokine-based therapeutic against inflammation. In this overview, recent developments for chemokines and for the chemokine-like factor MIF (macrophage migration inhibitory factor) will be discussed.

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MicroRNAs as Therapeutic Targets and Clinical Biomarkers in Atherosclerosis

Journal of Clinical Medicine ◽

10.3390/jcm8122199 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2199 ◽

Cited By ~ 8

Author(s):

Emma L. Solly ◽

Catherine G. Dimasi ◽

Christina A. Bursill ◽

Peter J. Psaltis ◽

Joanne T. M. Tan

Keyword(s):

Cardiovascular Disease ◽

Therapeutic Targets ◽

Holistic Approach ◽

Cell Types ◽

Atherosclerotic Cardiovascular Disease ◽

Cellular Mechanisms ◽

Cellular Effects ◽

Clinical Biomarkers ◽

Current Therapies ◽

Multiple Cell

Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Atherosclerosis develops over several decades and is mediated by a complex interplay of cellular mechanisms that drive a chronic inflammatory milieu and cell-to-cell interactions between endothelial cells, smooth muscle cells and macrophages that promote plaque development and progression. While there has been significant therapeutic advancement, there remains a gap where novel therapeutic approaches can complement current therapies to provide a holistic approach for treating atherosclerosis to orchestrate the regulation of complex signalling networks across multiple cell types and different stages of disease progression. MicroRNAs (miRNAs) are emerging as important post-transcriptional regulators of a suite of molecular signalling pathways and pathophysiological cellular effects. Furthermore, circulating miRNAs have emerged as a new class of disease biomarkers to better inform clinical diagnosis and provide new avenues for personalised therapies. This review focusses on recent insights into the potential role of miRNAs both as therapeutic targets in the regulation of the most influential processes that govern atherosclerosis and as clinical biomarkers that may be reflective of disease severity, highlighting the potential theranostic (therapeutic and diagnostic) properties of miRNAs in the management of cardiovascular disease.

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Faculty Opinions recommendation of Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727737949.793535337 ◽

2017 ◽

Author(s):

Alex Hoischen

Keyword(s):

Cardiovascular Disease ◽

Atherosclerotic Cardiovascular Disease ◽

Clonal Hematopoiesis

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Pigment Epithelium-Derived Factor: A Novel Therapeutic Target for Cardiometabolic Diseases and Related Complications

Current Medicinal Chemistry ◽

10.2174/0929867324666170608103140 ◽

2018 ◽

Vol 25 (13) ◽

pp. 1480-1500 ◽

Cited By ~ 7

Author(s):

Sho-ichi Yamagishi ◽

Takanori Matsui

Keyword(s):

Cardiovascular Disease ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Visceral Obesity ◽

Retinal Pigment Epithelial Cells ◽

Atherosclerotic Cardiovascular Disease ◽

Cardiometabolic Diseases ◽

The Metabolic Syndrome ◽

Pigment Epithelium Derived Factor ◽

Cardiometabolic Disorders

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert antithrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications. Furthermore, accumulating evidence has suggested that circulating PEDF levels may be a biomarker of severity and prognosis of these devastating disorders. Number of subjects with visceral obesity and insulin resistance is increasing, and the metabolic syndrome and its related complications, such as diabetes, nonalcoholic fatty liver disease/non-alcoholic steatohepatits, and atherosclerotic cardiovascular disease are a growing health challenge. Therefore, in this study, we review the pathophysiological role of PEDF in obesity and metabolic disorders, cardiovascular disease, diabetic eye and kidney complications, liver diseases, and reproductive system disorders, and discuss the potential clinical utility of modulating the expression and actions of PEDF for preventing these cardiometabolic disorders. We also refer to the clinical value of PEDF as a biomarker in cardiometabolic complications.

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