Epigenetic Regulation of Macrophage Polarization in Cardiovascular Diseases

Komal, Sumra; Han, Shengna; Cui, Liu-Gen; Zhai, Miao-Miao; Zhou, Yuejiao; Wang, Pei; Shakeel, Muhammad; Zhang, Lirong

doi:10.3390/ph16020141

Cited by 7 publications

(2 citation statements)

References 131 publications

(148 reference statements)

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“…Ongoing inflammatory insults [ 56 ], extracellular matrix deposition [ 57 ] and altered hemodynamics can trigger thrombus formation and rupture of the plaque, leading to myocardial infarction and ischemic stroke. The central role of monocytes in atherosclerosis, their recruitment and differentiation to foam cells has been greatly emphasized and targeted for the prevention of atherosclerosis [ 56 , 58 , 59 , 60 ].…”

Section: The Mononuclear Phagocytes Orchestrate Vascular Inflammation...mentioning

confidence: 99%

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

Rani

Marsche

2023

Pharmaceutics

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High-density lipoproteins (HDL) are complex endogenous nanoparticles involved in important functions such as reverse cholesterol transport and immunomodulatory activities, ensuring metabolic homeostasis and vascular health. The ability of HDL to interact with a plethora of immune cells and structural cells places it in the center of numerous disease pathophysiologies. However, inflammatory dysregulation can lead to pathogenic remodeling and post-translational modification of HDL, rendering HDL dysfunctional or even pro-inflammatory. Monocytes and macrophages play a critical role in mediating vascular inflammation, such as in coronary artery disease (CAD). The fact that HDL nanoparticles have potent anti-inflammatory effects on mononuclear phagocytes has opened new avenues for the development of nanotherapeutics to restore vascular integrity. HDL infusion therapies are being developed to improve the physiological functions of HDL and to quantitatively restore or increase the native HDL pool. The components and design of HDL-based nanoparticles have evolved significantly since their initial introduction with highly anticipated results in an ongoing phase III clinical trial in subjects with acute coronary syndrome. The understanding of mechanisms involved in HDL-based synthetic nanotherapeutics is critical to their design, therapeutic potential and effectiveness. In this review, we provide a current update on HDL-ApoA-I mimetic nanotherapeutics, highlighting the scope of treating vascular diseases by targeting monocytes and macrophages.

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Section: The Mononuclear Phagocytes Orchestrate Vascular Inflammation...mentioning

confidence: 99%

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

Rani

Marsche

2023

Pharmaceutics

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“…Epidemiological findings suggest that alcohol, obesity, smoking, hypertension, and coronary artery disease (CAD) are the risk factors for HF (3,4). At molecular level, the recent research suggests that ventricular remodeling, compensatory mechanisms, inflammatory signaling, fibrosis, oxidative stress, mitochondrial dysfunction, and epigenetic modifications, including RNA transcript modifications, are significantly associated with HF progression and predict HF outcomes (5).…”

Section: Introductionmentioning

confidence: 99%

ALKBH5 inhibitors as a potential treatment strategy in heart failure—inferences from gene expression profiling

Komal,

Gohar,

Althobaiti

et al. 2023

Front. Cardiovasc. Med.

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Heart Failure (HF) is a complex clinical syndrome in which the heart is unable to provide enough blood flow to meet metabolic needs and lacks efficient venous return. HF is a major risk factor for morbidity and mortality with cardiovascular diseases globally. Despite enormous research, the molecular markers relevant to disease prognosis and management remain not well understood. Here, we analyzed the whole transcriptomes of 18 failing hearts and 15 non-failing hearts (predominantly of Caucasian origin), by applying the standard in silico tools. The analyses revealed novel gene-markers including ALKBH5 of mRNA demethylation and KMT2E of histone modification processes, significantly over-expressed in the HF compared with the non-failing hearts (FDR < 0.05). To validate the over-expression of ALKBH5, we determined the global m6A level in hypoxic H9c2 cells using a dot blot assay. The global m6A level was found markedly lower in the hypoxic H9c2 cells than in the control cells. Additionally, the expression of ALKBH5 in the H9c2 cells was quantified by the qPCR and found to be 1.18 times higher at 12 h (p < 0.05), and 1.67 times higher at 24 h of hypoxia (p < 0.01) compared with the control cells, indicating a likely role of ALKBH5 in the failing cardiac cells. Furthermore, we identified several compounds through the virtual screening of 11,272 drug-like molecules of the ZINC15 database to inhibit the ALKBH5 in a molecular docking process. Collectively, the study revealed novel markers potentially involved in the pathophysiology of HF and suggested plausible therapeutic molecules for the management of the disease.

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