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European Journal of Pharmacology Sep 2015Atherosclerosis is a disease of the vascular wall that forms the basis for a large spectrum of pathologies of various organs and tissues. Although massive research... (Review)
Review
Atherosclerosis is a disease of the vascular wall that forms the basis for a large spectrum of pathologies of various organs and tissues. Although massive research efforts in the last decades have yielded valuable information about its underlying molecular mechanisms, this has not led to a translation into effective therapeutic interventions that can stop the progression or even can induce regression of atherosclerosis. This underscores the importance of investigations on the involvement of novel signaling pathways in the development and progression of this condition. In this review we focus on the role of Wnt signaling in atherosclerosis. Experimental evidence is presented that Wnt signaling is involved in many aspects of the development and progression of vascular lesions including endothelial dysfunction, macrophage activation and the proliferation and migration of vascular smooth muscle cells. Subsequently, we will discuss the role of Wnt signaling in myocardial infarction and stroke, two common pathologies resulting from the progression of atherosclerotic lesions towards an unstable phenotype. Despite the fact that the published data sometimes are ambiguous or even conflicting, a picture is emerging that an attenuation of Wnt signaling is beneficial for the cardiovascular system that is compromised by atherosclerosis.
Topics: Animals; Atherosclerosis; Humans; Plaque, Atherosclerotic; Wnt Signaling Pathway
PubMed: 25987418
DOI: 10.1016/j.ejphar.2015.05.023 -
Journal of the American College of... Sep 2021Plaque erosion, a distinct histopathological and clinical entity, accounts for over 30% of acute coronary syndromes (ACS). Optical coherence tomography allows in vivo... (Review)
Review
Plaque erosion, a distinct histopathological and clinical entity, accounts for over 30% of acute coronary syndromes (ACS). Optical coherence tomography allows in vivo diagnosis of plaque erosion. Local flow perturbation with activation of Toll-like receptor 2 and CD8 T cells and subsequent desquamation of endothelium and neutrophil extracellular trap formation contribute to mechanisms of plaque erosion. Compared with ACS patients with plaque rupture, those with plaque erosion are younger, have fewer traditional cardiovascular risk factors, have lower plaque burden, and are more likely to present with non-ST-segment elevation ACS. Early evidence suggests that in patients with ACS caused by plaque erosion, antithrombotic therapy without stenting may be a safe and effective option. Future randomized trials are needed to validate these findings. Clinical studies to develop noninvasive point-of-care biomarkers that distinguish plaque rupture from erosion, and to test novel therapies that target molecular pathways involved in plaque erosion are needed.
Topics: Acute Coronary Syndrome; Cardiac Imaging Techniques; Coronary Vessels; Humans; Plaque, Atherosclerotic; Tomography, Optical Coherence
PubMed: 34531028
DOI: 10.1016/j.jacc.2021.07.030 -
Future Cardiology Feb 2022Over the last decades, inflammation proved to play a pivotal role in atherosclerotic plaque formation, progression and destabilization. Several studies showed that the... (Review)
Review
Over the last decades, inflammation proved to play a pivotal role in atherosclerotic plaque formation, progression and destabilization. Several studies showed that the patients presenting with acute coronary syndrome are at increased risk of adverse cardiovascular events at both short- and long-term follow-up. Results from different clinical trials highlighted that a residual inflammatory risk exist and targeting inflammation is a successful strategy in selected cases associated to an increased inflammatory burden. Recently, the optimization of intracoronary and multimodality imaging allowed to also assess the entity of local inflammation, thus encouraging the individuation of plaque characteristics that portend a higher risk of future cardiovascular events. In this short review, we aim to highlight the role of systemic and local inflammation in acute coronary syndromes, to provide a summarized overview of the possible medical strategies applicable in selected cases and to underline the diagnostic and prognostic potential of multimodality imaging.
Topics: Acute Coronary Syndrome; Coronary Artery Disease; Humans; Inflammation; Plaque, Atherosclerotic; Treatment Outcome
PubMed: 34397269
DOI: 10.2217/fca-2021-0032 -
Arteriosclerosis, Thrombosis, and... Apr 2019Atherosclerosis is the leading cause of cardiovascular morbidity and mortality. Over the past 2 decades, increasing research attention is converging on the early... (Review)
Review
Atherosclerosis is the leading cause of cardiovascular morbidity and mortality. Over the past 2 decades, increasing research attention is converging on the early detection and monitoring of atherosclerotic plaque. Among several invasive and noninvasive imaging modalities, magnetic resonance imaging (MRI) is emerging as a promising option. Advantages include its versatility, excellent soft tissue contrast for plaque characterization and lack of ionizing radiation. In this review, we will explore the recent advances in multicontrast and multiparametric imaging sequences that are bringing the aspiration of simultaneous arterial lumen, vessel wall, and plaque characterization closer to clinical feasibility. We also discuss the latest advances in molecular magnetic resonance and multimodal atherosclerosis imaging.
Topics: Carotid Arteries; Carotid Artery Diseases; Contrast Media; Coronary Angiography; Coronary Artery Disease; Forecasting; Gadolinium; Humans; Magnetic Resonance Angiography; Metal Nanoparticles; Multimodal Imaging; Plaque, Atherosclerotic; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography
PubMed: 30760017
DOI: 10.1161/ATVBAHA.118.311754 -
Cell Death & Disease May 2021Atherosclerotic plaque vulnerability and rupture increase the risk of acute coronary syndromes. Advanced lesion macrophage apoptosis plays important role in the rupture...
Atherosclerotic plaque vulnerability and rupture increase the risk of acute coronary syndromes. Advanced lesion macrophage apoptosis plays important role in the rupture of atherosclerotic plaque, and endoplasmic reticulum stress (ERS) has been proved to be a key mechanism of macrophage apoptosis. Intermedin (IMD) is a regulator of ERS. Here, we investigated whether IMD enhances atherosclerotic plaque stability by inhibiting ERS-CHOP-mediated apoptosis and subsequent inflammasome in macrophages. We studied the effects of IMD on features of plaque vulnerability in hyperlipemia apolipoprotein E-deficient (ApoE) mice. Six-week IMD infusion significantly reduced atherosclerotic lesion size. Of note, IMD lowered lesion macrophage content and necrotic core size and increased fibrous cap thickness and vascular smooth muscle cells (VSMCs) content thus reducing overall plaque vulnerability. Immunohistochemical analysis indicated that IMD administration prevented ERS activation in aortic lesions of ApoE mice, which was further confirmed in oxidized low-density lipoproteins (ox-LDL) induced macrophages. Similar to IMD, taurine (Tau), a non-selective ERS inhibitor significantly reduced atherosclerotic lesion size and plaque vulnerability. Moreover, C/EBP-homologous protein (CHOP), a pro-apoptosis transcription factor involved in ERS, was significantly increased in advanced lesion macrophages, and deficiency of CHOP stabilized atherosclerotic plaques in AopE mice. IMD decreased CHOP level and apoptosis in vivo and in macrophages treated with ox-LDL. In addition, IMD infusion ameliorated NLRP3 inflammasome and subsequent proinflammatory cytokines in vivo and in vitro. IMD may attenuate the progression of atherosclerotic lesions and plaque vulnerability by inhibiting ERS-CHOP-mediated macrophage apoptosis, and subsequent NLRP3 triggered inflammation. The inhibitory effect of IMD on ERS-induced macrophages apoptosis was probably mediated by blocking CHOP activation.
Topics: Animals; Apoptosis; Humans; Inflammasomes; Macrophages; Mice; Neuropeptides; Peptide Fragments; Plaque, Atherosclerotic
PubMed: 33934111
DOI: 10.1038/s41419-021-03712-w -
European Journal of Clinical... Nov 2014Both pathophysiology and treatments of carotid atherosclerotic plaque stenosis represent two interesting fields of strong scientific investigation. Among different... (Review)
Review
BACKGROUND
Both pathophysiology and treatments of carotid atherosclerotic plaque stenosis represent two interesting fields of strong scientific investigation. Among different drugs, safety and efficacy of statin treatment have been widely investigated and proved.
MATERIALS AND METHODS
This narrative review is based on the material searched for and obtained via MEDLINE and PubMed up to March 2014. The search terms we used were: 'carotid plaque, intima-media thickness, plaque burden, stroke' in combination with 'statins, pleiotropic effects, HMG-CoA reductase inhibitors, lipid-lowering drugs'.
RESULTS
Carotid stenosis represents both a useful parameter to evaluate the atherosclerotic burden and a target for therapeutic (medical or surgical) decisions. Statins do not only improve the lipid profile, but also induce some 'pleiotropic' anti-inflammatory activities that contribute to carotid plaque stabilization. Statin-mediated protective activities are under active investigation at subclinical levels with the potential benefit of advanced imaging techniques. However, considering that some new techniques (excepted B-mode ultrasound) remain quite expensive, they can have for the moment an important role in research, but not in the clinical field.
CONCLUSIONS
Emerging evidence suggests that statin treatment improves carotid atherosclerosis, inducing a partial regression of plaque inflammation and size. Innovative imaging techniques might also ameliorate the identification of patients at high risk of cerebrovascular and coronary events, for which preventive statin treatments might be essential.
Topics: Carotid Intima-Media Thickness; Carotid Stenosis; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Magnetic Resonance Imaging; Plaque, Atherosclerotic; Randomized Controlled Trials as Topic; Tomography, Emission-Computed, Single-Photon
PubMed: 25231921
DOI: 10.1111/eci.12340 -
BioMed Research International 2017The leading cause of death worldwide is cardiovascular disease. Among the conditions related to the term, the most prominent one is the development of atherosclerotic... (Review)
Review
The leading cause of death worldwide is cardiovascular disease. Among the conditions related to the term, the most prominent one is the development of atherosclerotic plaques in the walls of arteries. The situation gets even worse with the fact that the plaque development may stay asymptomatic for a prolonged period of time. When it manifests as a cardiovascular disorder, it is already too late: the unfortunate individual is prescribed with a plethora of synthetic drugs, which are of debatable efficacy in the prevention of atherosclerotic lesions and safety. Cell models could be useful for the purpose of screening substances potentially effective against atherosclerosis progression and effective in reduction of already present plaques. In this overview, we present studies making use of in vitro and ex vivo models of atherosclerosis development that can prove valuable for clinical applications.
Topics: Animals; Atherosclerosis; Humans; Models, Biological; Plaque, Atherosclerotic
PubMed: 28286766
DOI: 10.1155/2017/5198723 -
Molecules (Basel, Switzerland) Aug 2023Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of...
Atherosclerosis is a multifactorial, progressive, chronic inflammatory disease. Ultrasound and magnetic resonance imaging are the most accurate predictors of atherosclerotic plaque instability (MRI). Cytokines such as osteopontin, osteoprotegerin, and metalloproteinase 9 could be used as the most recent markers to identify and track the efficacy of anti-atherosclerotic therapy. Patients with USG and MRI-verified unstable atherosclerotic plaque were included in the study. Biomarker concentrations were measured and compared before and after PCSK9 inhibitor therapy. Additionally, concentrations prior to treatment were correlated with MRI images of the carotid artery. After treatment with alirocumab, the concentrations of MMP-9 ( < 0.01) and OPN, OPG ( < 0.05) decreased significantly. Furthermore, the results of OPN, OPG, and MMP 9 varied significantly depending on the type of atherosclerotic plaque in the MRI assay. In stable atherosclerotic plaques, the concentrations of OPN and OPG were greater ( < 0.01), whereas the concentration of MMP9 correlated with the instability of the plaque ( < 0.05). We demonstrated, probably for the first time, that alirocumab therapy significantly decreased the serum concentration of atherosclerotic plaque markers. In addition, we demonstrated the relationship between the type of atherosclerotic plaque as determined by carotid MRI and the concentration of these markers.
Topics: Humans; Plaque, Atherosclerotic; Proprotein Convertase 9; Atherosclerosis; Ultrasonography
PubMed: 37570897
DOI: 10.3390/molecules28155928 -
Current Medicinal Chemistry 2015Although the understanding the pathophysiology of atherogenesis and atherosclerosis progression has been one of the major goals of cardiovascular research during the... (Review)
Review
The atherosclerotic plaque vulnerability: focus on the oxidative and endoplasmic reticulum stress in orchestrating the macrophage apoptosis in the formation of the necrotic core.
Although the understanding the pathophysiology of atherogenesis and atherosclerosis progression has been one of the major goals of cardiovascular research during the last decades, the precise mechanisms underlying plaque destabilization are still unknown. The disruption of the plaque and the thrombosis in the lumen that are mostly determined by the expansion of the necrotic core (NC) are driven by various mechanisms, including accelerated macrophage apoptosis and defective phagocytic clearance (defective efferocytosis). Oxidative stress is implicated in the expansion of the NC: in fact, many oxidized compounds and processes contribute to the macrophage apoptosis; in addition, the oxidized derivatives of polyunsatured fatty acids promote defective efferocytosis, with the final result of NC expansion. In the last years the role of the endoplasmic reticulum (ER) stress is under investigation to better define its possible contribution in affecting the NC expansion. The abnormal amount of apoptotic cells in the vulnerable plaque has been demonstrated to be related both to the sustained ER stress and to the expression of survival and protective genes, such as the unfolded protein response or/and the nuclear erytroid- related factor 2. In this review the authors focus on the promising results of the oxidative and ER stress in contributing to triggering and orchestrating the atherosclerotic plaque vulnerability.
Topics: Animals; Apoptosis; Endoplasmic Reticulum Stress; Humans; Macrophages; Necrosis; Oxidative Stress; Plaque, Atherosclerotic
PubMed: 25760090
DOI: 10.2174/0929867322666150311150829 -
The Journal of Physiology Jun 2016Epidemiological evidence conclusively demonstrates that calcium burden is a significant predictor of cardiovascular morbidity and mortality; however, the underlying... (Review)
Review
Epidemiological evidence conclusively demonstrates that calcium burden is a significant predictor of cardiovascular morbidity and mortality; however, the underlying mechanisms remain largely unknown. These observations have challenged the previously held notion that calcification serves to stabilize the atherosclerotic plaque. Recent studies have shown that microcalcifications that form within the fibrous cap of the plaques lead to the accrual of plaque-destabilizing mechanical stress. Given the association between calcification morphology and cardiovascular outcomes, it is important to understand the mechanisms leading to calcific mineral deposition and growth from the earliest stages. We highlight the open questions in the field of cardiovascular calcification and include a review of the proposed mechanisms involved in extracellular vesicle-mediated mineral deposition.
Topics: Animals; Calcinosis; Cardiovascular Diseases; Humans; Plaque, Atherosclerotic
PubMed: 27040360
DOI: 10.1113/JP271339