Sex-Specific Features of Calcific Aortic Valve Disease

Summerhill, Volha I; Moschetta, Donato; Orekhov, Alexander N.; Poggio, Paolo; Myasoedova, Veronika A.

doi:10.3390/ijms21165620

Cited by 50 publications

(39 citation statements)

References 90 publications

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“…Functionally, these smaller chamber compliance of adult males may be cardioprotective, by allowing the cardiac wall to counteract the increased haemodynamic stress encountered during high cardiac load [ 78 ]. Regardless, the sex-specific diastolic cardiac outputs (males lower than females) in adults is in agreement with the ventricular size differences in adult zebrafish [ 8 , 30 ], and wall thickness [ 79 ] and changes in cardiomyocyte contractile properties [ 80 ] in humans.…”

Section: Discussionsupporting

confidence: 74%

Embryonic Onset of Sexually Dimorphic Heart Rates in the Viviparous Fish, Gambusia holbrooki

2021

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In fish, little is known about sex-specific differences in physiology and performance of the heart and whether these differences manifest during development. Here for the first time, the sex-specific heart rates during embryogenesis of Gambusia holbrooki, from the onset of the heart rates (HRs) to just prior to parturition, was investigated using light cardiogram. The genetic sex of the embryos was post-verified using a sex-specific genetic marker. Results reveal that heart rates and resting time significantly increase (p < 0.05) with progressive embryonic development. Furthermore, both ventricular and atrial frequencies of female embryos were significantly higher (p < 0.05) than those of their male sibs at the corresponding developmental stages and remained so at all later developmental stages (p < 0.05). In concurrence, the heart rate and ventricular size of the adult females were also significantly (p < 0.05) higher and larger respectively than those of males. Collectively, the results suggest that the cardiac sex-dimorphism manifests as early as late-organogenesis and persists through adulthood in this species. These findings suggest that the cardiac measurements can be employed to non-invasively sex the developing embryos, well in advance of when their phenotypic sex is discernible. In addition, G. holbrooki could serve as a better model to study comparative vertebrate cardiovascular development as well as to investigate anthropogenic and climatic impacts on heart physiology of this species, that may be sex influenced.

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Section: Discussionsupporting

confidence: 74%

Embryonic Onset of Sexually Dimorphic Heart Rates in the Viviparous Fish, Gambusia holbrooki

2021

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“…There was a positive relationship between the severity, number and duration of cardiac risk factors, and risk of DAS [ 6 ]. Moreover, gender plays an important role in DAS pathogenesis, development and progression of valvular calcification processes, fibrosis, and hemodynamic severity, left ventricle hypertrophy, and cardiovascular outcomes in men and women [ 18 , 19 ]. Patients with DAS are often older and have more cardiovascular risk factors, systemic hypertension and atherosclerosis, which all show association with increased aortic stiffness and cognitive decline [ 20 , 21 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Importance of Increased Arterial Resistance in Risk Prediction in Patients with Cardiovascular Risk Factors and Degenerative Aortic Stenosis

Baran

Kleczyński

Niewiara

et al. 2021

JCM

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Background: Cardiovascular disease is a leading cause of heart failure (HF) and major adverse cardiac and cerebral events (MACCE). Objective: To evaluate impact of vascular resistance on HF and MACCE incidence in subjects with cardiovascular risk factors (CRF) and degenerative aortic valve stenosis (DAS). Methods: From January 2016 to December 2018, in 404 patients with cardiovascular disease, including 267 patients with moderate-to-severe DAS and 137 patients with CRF, mean values of resistive index (RI) and pulsatile index (PI) were obtained from carotid and vertebral arteries. Patients were followed-up for 2.5 years, for primary outcome of HF and MACCE episodes. Results: RI and PI values in patients with DAS compared to CRF were significantly higher, with optimal cut-offs discriminating arterial resistance of ≥0.7 for RI (sensitivity: 80.5%, specificity: 78.8%) and ≥1.3 for PI (sensitivity: 81.3%, specificity: 79.6%). Age, female gender, diabetes, and DAS were all independently associated with increased resistance. During the follow-up period, 68 (16.8%) episodes of HF-MACCE occurred. High RI (odds ratio 1.25, 95% CI 1.13–1.37) and PI (odds ratio 1.21, 95% CI 1.10–1.34) were associated with risk of HF-MACCE. Conclusions: An accurate assessment of vascular resistance may be used for HF-MACCE risk stratification in patients with DAS.

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“…In vitro , male VICs showed a higher alkaline phosphatase content and higher propensity for calcification ( 76 ). Sex-specific features and mechanisms in CAVD have been reviewed extensively before ( 78 , 79 ). Of note, most reports focus on calcification as the primary outcome, and little is known about sex-dependent differential effects on fibrosis.…”

Section: Patterns In the Cellular Contribution Temporal Onset And Risk Factors For Valvular Fibrosismentioning

confidence: 99%

Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis

Büttner

Feistner

Lurz

et al. 2021

Front. Cardiovasc. Med.

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Calcific aortic valve disease (CAVD) is a highly prevalent and progressive disorder that ultimately causes gradual narrowing of the left ventricular outflow orifice with ensuing devastating hemodynamic effects on the heart. Calcific mineral accumulation is the hallmark pathology defining this process; however, fibrotic extracellular matrix (ECM) remodeling that leads to extensive deposition of fibrous connective tissue and distortion of the valvular microarchitecture similarly has major biomechanical and functional consequences for heart valve function. Significant advances have been made to unravel the complex mechanisms that govern these active, cell-mediated processes, yet the interplay between fibrosis and calcification and the individual contribution to progressive extracellular matrix stiffening require further clarification. Specifically, we discuss (1) the valvular biomechanics and layered ECM composition, (2) patterns in the cellular contribution, temporal onset, and risk factors for valvular fibrosis, (3) imaging valvular fibrosis, (4) biomechanical implications of valvular fibrosis, and (5) molecular mechanisms promoting fibrotic tissue remodeling and the possibility of reverse remodeling. This review explores our current understanding of the cellular and molecular drivers of fibrogenesis and the pathophysiological role of fibrosis in CAVD.

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Sex-Specific Features of Calcific Aortic Valve Disease

Cited by 50 publications

References 90 publications

Embryonic Onset of Sexually Dimorphic Heart Rates in the Viviparous Fish, Gambusia holbrooki

Embryonic Onset of Sexually Dimorphic Heart Rates in the Viviparous Fish, Gambusia holbrooki

Importance of Increased Arterial Resistance in Risk Prediction in Patients with Cardiovascular Risk Factors and Degenerative Aortic Stenosis

Dissecting Calcific Aortic Valve Disease—The Role, Etiology, and Drivers of Valvular Fibrosis

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