Molecular Mechanisms of Cardiovascular Remodeling

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 5334

Special Issue Editor


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Guest Editor
Laboratory of Cardiovascular Science, National Institute on Aging/National Institutes of Health, Baltimore, MD 21224, USA
Interests: aging; cardiovascular disease; cardiovascular information and remodeling

Special Issue Information

Dear Colleagues,

The study of the cellular and molecular mechanisms underlying arterial aging is an important subject in geriatric cardiology. As the global population ages, life expectancy is increasingly limited by poor interventions for adverse cardiovascular conditions associated with aging. Cardiovascular conditions that decline with age negatively impact the health- and lifespans.

Cardiovascular aging, primarily attributed to a proinflammatory process that likely begins at birth, leads to harmful effects on the cardiovascular structural and functional system. It is a major risk factor for key cardiovascular diseases such as hypertension, atherosclerosis, heart failure, and cerebrovascular cognitive decline and dementia.

With aging, the cardiovascular system develops a pro-inflammatory microenvironment, marked by an increase in pro-inflammatory chemokines and cytokines such as NF-κB, and a decrease in their anti-inflammatory counterparts such as NrF-2. The disruption of the balance in inflammatory regulatory networks is a crucial driver of cardiovascular aging, setting a stage for the onset and progression of hypertension, atherosclerosis, heart failure, and age-related cognitive decline and dementia.

Age-associated disorders in pro-inflammatory signaling pathways in the cardiovascular micro-environment lead to significant changes in the expression and function of proteins, mRNA, micro-RNA and long-noncoding RNA in the cardiovascular system. These include vascular endothelial and smooth muscle cells, cardiomyocytes, cardiac nonmyocytes such as fibroblasts, and the cardiovascular extracellular matrix.

As age advances, low-grade chronic inflammation increases cardiovascular cell senescence and decreases their regenerative/repair capacity. In the cardiovascular system, this results in increased proliferation, apoptosis, migration and invasion of vascular smooth muscle cells, and inflammatory modifications of the cardiomyocytes and extracellular matrix. In the heart, age-associated proinflammation leads to a decrease in the number of cardiomyocytes and an increase in the number of noncardiomyocytes such as fibroblasts, mast cells, T and B cells, and macrophages.

Furthermore, cardiovascular cells develop age-associated secretory phenotypes, leading to pathological vascular matrix stiffening due to increased accumulation, deposition, degradation and misfolding/modification of the extracellular matrix. These interactions between cardiovascular cells and the aged microenvironment result in a pro-inflammatory cascade, known as either the age-associated cardiovascular secretory phenotype (ACSP) or the senescence-associated secretory phenotype (SASP). Both promote senescence-associated protein degradation or modification, facilitating disorders of cardiovascular cellular homeostasis.

Hypertension, atherosclerosis and heart failure are not only the leading causes of death in the elderly but also major causes of disability and dependency. They result in myocardial ischemia and infarction, cardiac dysfunction, and cardiac arrhythmias in coronary and peripheral arterial system. In the cerebrovascular system, they contribute to stroke, dementia and potentially Alzheimer’s disease. In the aorta, hypertension and atherosclerosis are associated with aneurysm and peripheral arterial disease, leading to skeletal muscle atrophy, known as sarcopenia.

In advanced lesions, senescent cells release atherogenic and inflammatory cytokines and chemokines, enhancing plaque instability and leading to the degeneration of elastic fibers and vulnerability of the fibrous cap. These findings not only suggest that senescent cells play a crucial role in the formation, maturation and frailty of atheroma, but also imply that the selective removal of these cells and their aftereffects through senolytic approaches could be a promising strategy for treating hypertension, atherosclerosis, heart failure and even Alzheimer’s disease in older adults.

In this Special Issue, our goal is to provide an updated overview of the cellular and molecular mechanisms influencing cardiovascular inflammation and the structural and functional aging of the cardiovascular system.

We believe that this Special Issue will enhance our understanding of the pathogenesis of chronic or age-related cardiovascular diseases such as hypertension, atherosclerosis and vasculopathy. It will also provide updates on their treatment with both existing and emerging therapeutic approaches.

Dr. Mingyi Wang
Guest Editor

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Keywords

  • vascular remodeling aging
  • extracellular matrix
  • atherosclerosis peripheral
  • artery disease
  • chronic heart failure
  • cardiovascular associated cognitive decline

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Published Papers (2 papers)

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18 pages, 24081 KiB  
Review
Unraveling Elastic Fiber-Derived Signaling in Arterial Aging and Related Arterial Diseases
by Mingyi Wang, Kimberly R. McGraw, Robert E. Monticone and Gianfranco Pintus
Biomolecules 2025, 15(2), 153; https://doi.org/10.3390/biom15020153 - 21 Jan 2025
Cited by 1 | Viewed by 1917
Abstract
Arterial stiffening is a significant risk factor for the development of cardiovascular diseases, including hypertension, atherosclerosis, and arteriopathy. The destruction of elastic fibers, accompanied by vascular inflammatory remodeling, is a key process in the progression of arterial stiffening and related pathologies. In young, [...] Read more.
Arterial stiffening is a significant risk factor for the development of cardiovascular diseases, including hypertension, atherosclerosis, and arteriopathy. The destruction of elastic fibers, accompanied by vascular inflammatory remodeling, is a key process in the progression of arterial stiffening and related pathologies. In young, healthy arteries, intact elastic fibers create a resilient microenvironment that maintains the quiescence of arterial cells. However, with advancing age, these elastic fibers undergo post-translational modifications, such as oxidation, glycosylation, and calcification, leading to their eventual degeneration. This degeneration results in the release of degraded peptides and the formation of an inflammatory, stiffened niche. Elastic fiber degeneration profoundly impacts the proinflammatory phenotypes and behaviors of various arterial cells, including endothelial cells, smooth muscle cells, macrophages, fibroblasts, and mast cells. Notably, the degraded elastic fibers release elastin-derived peptides (EDPs), which act as potent inflammatory molecules. EDPs activate various arterial cellular processes, including inflammatory secretion, cell migration, proliferation, and calcification, by interacting with the elastin receptor complex (ERC). These elastin-related cellular events are commonly observed with aging and in diseased arteries. These findings suggest that the degeneration of the elastic fiber meshwork is a primary event driving arterial inflammation, stiffening, and adverse remodeling with advancing age. Therefore, preserving elastic fibers and blocking the EDP/ERC signaling pathways may offer promising therapeutic strategies for mitigating age-related arterial remodeling and related arterial diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Cardiovascular Remodeling)
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18 pages, 3397 KiB  
Perspective
Tetrahydrobiopterin in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Friend or Foe?
by A. F. M. Towheedur Rahman, Anna Benko, Sarojini Bulbule, Carl Gunnar Gottschalk, Leggy A. Arnold and Avik Roy
Biomolecules 2025, 15(1), 102; https://doi.org/10.3390/biom15010102 - 10 Jan 2025
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Abstract
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a chronic multisystem disease characterized by severe muscle fatigue, pain, dizziness, and brain fog. The two most common symptoms are post-exertional malaise (PEM) and orthostatic intolerance (OI). ME/CFS patients with OI (ME+OI) suffer from dizziness [...] Read more.
Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS) is a chronic multisystem disease characterized by severe muscle fatigue, pain, dizziness, and brain fog. The two most common symptoms are post-exertional malaise (PEM) and orthostatic intolerance (OI). ME/CFS patients with OI (ME+OI) suffer from dizziness or faintness due to a sudden drop in blood pressure while maintaining an upright posture. Clinical research has demonstrated that patients with OI display severe cardiovascular abnormalities resulting in reduced effective blood flow in the cerebral blood vessels. However, despite intense investigation, it is not known why the effective cerebral blood flow is reduced in OI patients. Based on our recent findings, we observed that tetrahydrobiopterin (BH4) metabolism was highly dysregulated in ME+OI patients. In the current review article, we attempted to summarize our recent findings on BH4 metabolism to shed light on the molecular mechanisms of OI. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Cardiovascular Remodeling)
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