Anti-inflammatory therapy for cardiovascular disease

Kosmas, Constantine E.; Silverio, Delia; Sourlas, Andreas; Montan, Peter D; Guzman, Eliscer; García, Mario J.

doi:10.21037/atm.2019.02.34

Cited by 55 publications

(38 citation statements)

References 56 publications

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“…Thanks to these results, inflammation regained the attention as possible point of therapeutic intervention for atherosclerosis treatment. However, it appeared to be more promising to target specific proinflammatory pathways rather than inflammation in general [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Signaling Pathways and Key Genes Involved in Regulation of foam Cell Formation in Atherosclerosis

Poznyak

Melnichenko

et al. 2020

Cells

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Atherosclerosis is associated with acute cardiovascular conditions, such as ischemic heart disease, myocardial infarction, and stroke, and is the leading cause of morbidity and mortality worldwide. Our understanding of atherosclerosis and the processes triggering its initiation is constantly improving, and, during the last few decades, many pathological processes related to this disease have been investigated in detail. For example, atherosclerosis has been considered to be a chronic inflammation triggered by the injury of the arterial wall. However, recent works showed that atherogenesis is a more complex process involving not only the immune system, but also resident cells of the vessel wall, genetic factors, altered hemodynamics, and changes in lipid metabolism. In this review, we focus on foam cells that are crucial for atherosclerosis lesion formation. It has been demonstrated that the formation of foam cells is induced by modified low-density lipoprotein (LDL). The beneficial effects of the majority of therapeutic strategies with generalized action, such as the use of anti-inflammatory drugs or antioxidants, were not confirmed by clinical studies. However, the experimental therapies targeting certain stages of atherosclerosis, among which are lipid accumulation, were shown to be more effective. This emphasizes the relevance of future detailed investigation of atherogenesis and the importance of new therapies development.

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Section: Introductionmentioning

confidence: 99%

Signaling Pathways and Key Genes Involved in Regulation of foam Cell Formation in Atherosclerosis

Poznyak

Melnichenko

et al. 2020

Cells

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“…Lipid accumulation and in ammation response in the vascular wall were involved in the occurrence and progression of atherosclerosis [30,31]. During this pathological process, blood monocytes were considered as an important determiner based on the fact that they migrated into the plaque areas and differentiated into macrophages which could turn to foam cells by swallowing a large amount of lipids and polarize to M1-like phenotype when exposed to the atherosclerotic micro-environment [32].…”

Section: Discussionmentioning

confidence: 99%

Rosuvastatin Inhibits Atherosclerosis Development by Improving Lipid Accumulation and Polarization Conversion of Macrophages via Regulating Autophagy

Zhang¹,

Qin²,

Wan³

et al. 2020

Preprint

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Background Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions. Methods All male Apolipoprotein E-deficient (ApoE-/-) mice were fed high-fat diet supplemented with RVS (10mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages.Results Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE-/- mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively. Conclusions Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.

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“…Although inflammation is a basic defense mechanism of the human body, persistently elevated values of some inflammatory markers considerably affect the development and prognosis of cardiovascular diseases. 18 It was reported that calprotectin catalyzes the formation of reactive oxygen species by activating NADPH oxidase, as well as is involved in the pathogenesis of atherosclerosis by interacting with the receptor for advanced glycation end products and the toll -like receptor and by accelerating the signaling pathway. 13 Katashima et al 19 reported high serum calprotectin levels in patients with acute myocardial infarction.…”

Section: Methods Study Design and Populationmentioning

confidence: 99%

Relationship of serum calprotectin, angiopoietin‑1, and angiopoietin‑2 levels with coronary collateral circulation in patients with stable coronary artery disease

et al. 2019

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BACKGROUND In patients with chronic stable coronary artery disease (CAD), well-developed coronary collateral circulation (CCC) is known to reduce long-term mortality. AIMS The objective of this study was to determine the relationship of serum calprotectin (S100A8 / S100A9), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) concentrations with CCC in patients with stable CAD. METHODS This prospective cross-sectional study included 147 patients with stable angina pectoris. The Cohen-Rentrop classification was used to assess CCC. Patients were divided into 2 groups: with poor CCC (Cohen-Rentrop score, 0-1; n = 79) and with good CCC (Cohen-Rentrop score, 2-3; n = 68). Serum calprotectin, Ang-1, and Ang-2 concentrations were compated between groups. RESULTS Compared with the group with good CCC, serum calprotectin and Ang-1 levels were higher (P <0.01 and P <0.001, respectively), while serum Ang-2 levels were lower (P <0.01) in the poor-CCC group. C-reactive protein levels showed a moderate positive correlation with calprotectin levels (r = 0.359; P <0.001). In a multivariate regression analysis, only calprotectin (P <0.05) and Ang-1 (P <0.05) were found to be independent predictors of good and poor CCC. CONCLUSIONS Our study showed that Ang-2 levels were lower, while serum calprotectin and Ang-1 levels were higher, in patients with stable CAD and poor CCC regardless of the complexity and severity of coronary arteriosclerosis. If these results are confirmed in future studies, calprotectin may be considered a useful biomarker for guiding anti-ischemic treatment.

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Anti-inflammatory therapy for cardiovascular disease

Cited by 55 publications

References 56 publications

Signaling Pathways and Key Genes Involved in Regulation of foam Cell Formation in Atherosclerosis

Signaling Pathways and Key Genes Involved in Regulation of foam Cell Formation in Atherosclerosis

Rosuvastatin Inhibits Atherosclerosis Development by Improving Lipid Accumulation and Polarization Conversion of Macrophages via Regulating Autophagy

Relationship of serum calprotectin, angiopoietin‑1, and angiopoietin‑2 levels with coronary collateral circulation in patients with stable coronary artery disease

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