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Coronary flow reserve in degenerative aortic stenosis and diabetes mellitus: An intriguing question.Kardiologia Polska 2022
Topics: Humans; Aortic Valve Stenosis; Coronary Vessels; Diabetes Mellitus; Coronary Circulation; Coronary Stenosis; Fractional Flow Reserve, Myocardial; Blood Flow Velocity
PubMed: 36621014
DOI: 10.33963/KP.a2022.0256 -
Antioxidants & Redox Signaling Sep 2016Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In... (Review)
Review
SIGNIFICANCE
Currently, calcific aortic valve disease (CAVD) is only treatable through surgical intervention because the specific mechanisms leading to the disease remain unclear. In this review, we explore the forces and structure of the valve, as well as the mechanosensors and downstream signaling in the valve endothelium known to contribute to inflammation and valve dysfunction.
RECENT ADVANCES
While the valvular structure enables adaptation to dynamic hemodynamic forces, these are impaired during CAVD, resulting in pathological systemic changes. Mechanosensing mechanisms-proteins, sugars, and membrane structures-at the surface of the valve endothelial cell relay mechanical signals to the nucleus. As a result, a large number of mechanosensitive genes are transcribed to alter cellular phenotype and, ultimately, induce inflammation and CAVD. Transforming growth factor-β signaling and Wnt/β-catenin have been widely studied in this context. Importantly, NADPH oxidase and reactive oxygen species/reactive nitrogen species signaling has increasingly been recognized to play a key role in the cellular response to mechanical stimuli. In addition, a number of valvular microRNAs are mechanosensitive and may regulate the progression of CAVD.
CRITICAL ISSUES
While numerous pathways have been described in the pathology of CAVD, no treatment options are available to avoid surgery for advanced stenosis and calcification of the aortic valve. More work must be focused on this issue to lead to successful therapies for the disease.
FUTURE DIRECTIONS
Ultimately, a more complete understanding of the mechanisms within the aortic valve endothelium will lead us to future therapies important for treatment of CAVD without the risks involved with valve replacement or repair. Antioxid. Redox Signal. 25, 401-414.
Topics: Animals; Aortic Valve; Aortic Valve Stenosis; Biomarkers; Calcinosis; Endothelium; Gene Expression Regulation; Hemodynamics; Humans; Mechanoreceptors; Mechanotransduction, Cellular; Shear Strength; Stress, Mechanical
PubMed: 26651130
DOI: 10.1089/ars.2015.6554 -
Journal of the American College of... Apr 2020
Topics: Aortic Valve; Aortic Valve Stenosis; Female; Humans; Male
PubMed: 32327101
DOI: 10.1016/j.jacc.2020.03.026 -
JACC. Cardiovascular Imaging Mar 2023
Topics: Humans; Predictive Value of Tests; Aortic Valve Stenosis; Aortic Valve; Disease Progression
PubMed: 36752439
DOI: 10.1016/j.jcmg.2022.12.002 -
Singapore Medical Journal Sep 2018
Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Asian People; Cardiology; Cardiovascular Surgical Procedures; Female; Humans; Japan; Male; Middle Aged; Risk; Severity of Illness Index; Singapore
PubMed: 30128576
DOI: 10.11622/smedj.2018103 -
Trends in Cardiovascular Medicine Apr 2018Transcatheter aortic valve replacement (TAVR) revolutionized the treatment of severe symptomatic aortic stenosis (AS). TAVR is increasingly offered for lower-risk... (Review)
Review
Transcatheter aortic valve replacement (TAVR) revolutionized the treatment of severe symptomatic aortic stenosis (AS). TAVR is increasingly offered for lower-risk patients. The role and place of TAVR in the future treatment of AS is not clear yet. In this review, we discuss the long-term outlook for TAVR, its challenges and its relationship to conventional surgical aortic valve replacement.
Topics: Aortic Valve Stenosis; Clinical Decision-Making; Diffusion of Innovation; Forecasting; Humans; Patient Selection; Risk Factors; Severity of Illness Index; Time Factors; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 28838702
DOI: 10.1016/j.tcm.2017.08.004 -
Clinics in Geriatric Medicine May 2016Aortic stenosis is a disease of older adults; many have associated comorbidities. With the aging of the population and the emergence of transcatheter aortic valve... (Review)
Review
Aortic stenosis is a disease of older adults; many have associated comorbidities. With the aging of the population and the emergence of transcatheter aortic valve replacement as a treatment, clinicians will increasingly be confronted with aortic stenosis and multimorbidity, making the evaluation, management, and treatment of aortic stenosis more complex. To optimize patient-centered clinical outcomes, new treatment paradigms are needed that recognize the import and influence of multimorbidity on patients with aortic stenosis. The authors review the prevalence of medical and aging-related comorbidities in patients with aortic stenosis, their impact on outcomes, and discuss how they influence management and treatment decisions.
Topics: Aged; Aortic Valve Stenosis; Clinical Decision-Making; Comorbidity; Humans; Patient Outcome Assessment; Patient Selection; Transcatheter Aortic Valve Replacement
PubMed: 27113148
DOI: 10.1016/j.cger.2016.01.006 -
Journal of Interventional Cardiology 2020With the increasing prevalence of aortic stenosis (AS) due to a growing elderly population, a proper understanding of its physiology is paramount to guide therapy and... (Review)
Review
With the increasing prevalence of aortic stenosis (AS) due to a growing elderly population, a proper understanding of its physiology is paramount to guide therapy and define severity. A better understanding of the microvasculature in AS could improve clinical care by predicting left ventricular remodeling or anticipate the interplay between epicardial stenosis and myocardial dysfunction. In this review, we combine five decades of literature regarding microvascular, coronary, and aortic valve physiology with emerging insights from newly developed invasive tools for quantifying microcirculatory function. Furthermore, we describe the coupling between microcirculation and epicardial stenosis, which is currently under investigation in several randomized trials enrolling subjects with concomitant AS and coronary disease. To clarify the physiology explained previously, we present two instructive cases with invasive pressure measurements quantifying coexisting valve and coronary stenoses. Finally, we pose open clinical and research questions whose answers would further expand our knowledge of microvascular dysfunction in AS. These trials were registered with NCT03042104, NCT03094143, and NCT02436655.
Topics: Aged; Aortic Valve Stenosis; Coronary Artery Disease; Coronary Circulation; Disease Management; Humans; Microcirculation
PubMed: 32774184
DOI: 10.1155/2020/4603169 -
Biology of Sex Differences Oct 2023Aortic stenosis (AS) is characterized by inflammation, fibrosis, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is...
BACKGROUND
Aortic stenosis (AS) is characterized by inflammation, fibrosis, osteogenesis and angiogenesis. Men and women develop these mechanisms differently. Galectin-3 (Gal-3) is a pro-inflammatory and pro-osteogenic lectin in AS. In this work, we aim to analyse a potential sex-differential role of Gal-3 in AS.
METHODS
226 patients (61.50% men) with severe AS undergoing surgical aortic valve (AV) replacement were recruited. In AVs, Gal-3 expression and its relationship with inflammatory, osteogenic and angiogenic markers was assessed. Valve interstitial cells (VICs) were primary cultured to perform in vitro experiments.
RESULTS
Proteomic analysis revealed that intracellular Gal-3 was over-expressed in VICs of male AS patients. Gal-3 secretion was also higher in men's VICs as compared to women's. In human AVs, Gal-3 protein levels were significantly higher in men, with stronger immunostaining in VICs with myofibroblastic phenotype and valve endothelial cells. Gal-3 levels in AVs were positively correlated with inflammatory markers in both sexes. Gal-3 expression was also positively correlated with osteogenic markers mainly in men AVs, and with angiogenic molecules only in this sex. In vitro, Gal-3 treatment induced expression of inflammatory, osteogenic and angiogenic markers in male's VICs, while it only upregulated inflammatory and osteogenic molecules in women-derived cells. Gal-3 blockade with pharmacological inhibitors (modified citrus pectin and G3P-01) prevented the upregulation of inflammatory, osteogenic and angiogenic molecules.
CONCLUSIONS
Gal-3 plays a sex-differential role in the setting of AS, and it could be a new sex-specific therapeutic target controlling pathological features of AS in VICs.
Topics: Female; Humans; Male; Aortic Valve; Aortic Valve Stenosis; Endothelial Cells; Galectin 3; Proteomics
PubMed: 37875993
DOI: 10.1186/s13293-023-00556-1 -
Acta Cardiologica Feb 2016The coexistence of mitral and aortic stenosis is not exceptional. Whereas rheumatic fever is currently plummeting in the Western countries, the incidence of degenerative... (Review)
Review
The coexistence of mitral and aortic stenosis is not exceptional. Whereas rheumatic fever is currently plummeting in the Western countries, the incidence of degenerative disease is inversely increasing. The haemodynamic interactions which may interfere both with the usual echocardiographic parameters and with the invasive assessment may render the diagnosis difficult. The therapeutic challenges raised by this entity should not be underestimated. The increased morbidity and mortality of multivalvular surgery has to be balanced with the risk of a second operation down the line if one valvular involvement, deemed of a lesser importance, is neglected. This complex situation requires the multidisciplinary approach of a heart team involving surgeons, cardiologists, geriatrists if need be and imaging specialists.
Topics: Aortic Valve Stenosis; Heart Valve Prosthesis Implantation; Humans; Incidence; Italy; Mitral Valve Stenosis; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ultrasonography
PubMed: 26853247
DOI: 10.2143/AC.71.1.3132091