Molecular Mechanisms of Cardiovascular Remodeling

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the Special Issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.