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Inflammation as a New Therapeutic Target among Older Patients with Ischemic Heart Disease.

ABSTRACT: Cardiovascular (CV) diseases remain a global health challenge, with ischemic heart disease (IHD) being the primary cause of both morbidity and mortality. Despite optimal pharmacological therapy, older patients with IHD exhibit an increased susceptibility to recurrent ischemic events, significantly impacting their prognosis. Inflammation is intricately linked with the aging process and plays a pivotal role in the evolution of atherosclerosis. Emerging anti-inflammatory therapies have shown promise in reducing ischemic events among high-risk populations. This review aims to explore the potential of targeted anti-inflammatory interventions in improving clinical outcomes and the quality of life for older patients with IHD.

SUBMITTER: Maidana D

PROVIDER: S-EPMC10816645 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Inflammation as a New Therapeutic Target among Older Patients with Ischemic Heart Disease.

Maidana Daniela D Arroyo-Álvarez Andrea A Arenas-Loriente Andrea A Barreres-Martín Guillermo G Muñoz-Alfonso Carles C Bompart Berroteran Daznia D Esteve Claramunt Francisca F Blanco Del Burgo Regina R Cepas-Guillén Pedro P Garcia-Blas Sergio S Bonanad Clara C

Journal of clinical medicine 20240109 2

Cardiovascular (CV) diseases remain a global health challenge, with ischemic heart disease (IHD) being the primary cause of both morbidity and mortality. Despite optimal pharmacological therapy, older patients with IHD exhibit an increased susceptibility to recurrent ischemic events, significantly impacting their prognosis. Inflammation is intricately linked with the aging process and plays a pivotal role in the evolution of atherosclerosis. Emerging anti-inflammatory therapies have shown promis ...[more]

PMID: 38256497

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Project description:ObjectiveThere is growing recognition that adipose tissue-derived proatherogenic mediators contribute to obesity-related cardiovascular disease. We sought to characterize regional differences in perivascular adipose tissue (PVAT) phenotype in relation to atherosclerosis susceptibility. Approach and Results: We examined thoracic PVAT samples in 34 subjects (body mass index 32±6 kg/m2, age 59±11 years) undergoing valvular, aortic, or coronary artery bypass graft surgeries and performed transcriptomic characterization using whole-genome expression profiling and quantitative polymerase chain reaction analyses. We identified a highly inflamed region of PVAT surrounding the human aortic root in close proximity to coronary takeoff and adjoining epicardial fat. In subjects undergoing coronary artery bypass graft, we found 300 genes significantly upregulated (false discovery rate Q<0.1) in paired samples of PVAT surrounding the aortic root compared with nonatherosclerotic left internal mammary artery. Genes encoding proteins mechanistically implicated in atherogenesis were enriched in aortic PVAT consisting of signaling pathways linked to inflammation, WNT (wingless-related integration site) signaling, matrix remodeling, coagulation, and angiogenesis. Overexpression of several proatherogenic transcripts, including IL1β, CCL2 (MCP-1), and IL6, were confirmed by quantitative polymerase chain reaction and significantly bolstered in coronary artery disease subjects. Angiographic coronary artery disease burden quantified by the Gensini score positively correlated with the expression of inflammatory genes in PVAT. Moreover, periaortic adipose inflammation was markedly higher in obese subjects with striking upregulation (≈8-fold) of IL1β expression compared to nonobese individuals.ConclusionsProatherogenic mediators that originate from dysfunctional PVAT may contribute to vascular disease mechanisms in human vessels. Moreover, PVAT may adopt detrimental properties under obese conditions that play a key role in the pathophysiology of ischemic heart disease. Graphic Abstract: A graphic abstract is available for this article.

Project description:IntroductionAcute myocardial infarction (MI) is a primary cause of worldwide morbidity and mortality. Macrophages are fundamental components of post-MI inflammation. Pro-inflammatory macrophages can lead to adverse cardiac remodeling and heart failure while anti-inflammatory/reparative macrophages enhance tissue healing. Shifting the balance between pro-inflammatory and reparative macrophages post-MI is a novel therapeutic strategy. Azithromycin (AZM), a commonly used macrolide antibiotic, polarizes macrophages towards the anti-inflammatory phenotype, as shown in animal and human studies. We hypothesized that AZM modulates post-MI inflammation and improves cardiac recovery.Methods and resultsMale WT mice (C57BL/6, 6-8 weeks old) were treated with either oral AZM (160 mg/kg/day) or vehicle (control) starting 3 days prior to MI and continued to day 7 post-MI. We observed a significant reduction in mortality with AZM therapy. AZM-treated mice showed a significant decrease in pro-inflammatory (CD45+/Ly6G-/F4-80+/CD86+) and increase in anti-inflammatory (CD45+/Ly6G-/F4-80+/CD206+) macrophages, decreasing the pro-inflammatory/anti-inflammatory macrophage ratio in the heart and peripheral blood as assessed by flow cytometry and immunohistochemistry. Macrophage changes were associated with a significant decline in pro- and increase in anti-inflammatory cytokines. Mechanistic studies confirmed the ability of AZM to shift macrophage response towards an anti-inflammatory state under hypoxia/reperfusion stress. Additionally, AZM treatment was associated with a distinct decrease in neutrophil count due to apoptosis, a known signal for shifting macrophages towards the anti-inflammatory phenotype. Finally, AZM treatment improved cardiac recovery, scar size, and angiogenesis.ConclusionAzithromycin plays a cardioprotective role in the early phase post-MI through attenuating inflammation and enhancing cardiac recovery. Post-MI treatment and human translational studies are warranted to examine the therapeutic applications of AZM.

Dataset Information

Inflammation as a New Therapeutic Target among Older Patients with Ischemic Heart Disease.

Publications

Inflammation as a New Therapeutic Target among Older Patients with Ischemic Heart Disease.

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