Evolving Concepts of Cardiac Valve Dynamics

Abstract

Abstract-Considerable progress has been made in recent years toward elucidating a conceptual framework that integrates the dynamic functional structure, mechanical properties, and pathobiological behavior of the cardiac valves. This communication reviews the evolving paradigm of a continuum of heart valve structure, function, and pathobiology and explores its implications. Specifically, we discuss (1) the interactions of valve biology and biomechanics (eg, correlations of function with structure at the cell, tissue, and organ levels and mechanical considerations, development, endothelial cell and interstitial cell biology, extracellular matrix biology, homeostasis, and adaptation to environmental change); (2) Key Words: aortic valve Ⅲ mitral valve Ⅲ pathology Ⅲ prosthesis Ⅲ tissue engineering I mportant conceptual advances, new data, and evolution in our understanding and application of the principles underlying the dynamic functional, biological, and mechanical behavior of the cardiac valves have occurred in recent years. Research in heart valve biology and disease has been enabled by the availability of cultures of heart valve cells, computational methodology, the design and use of in vitro and in vivo experimental systems that model elements of valve biological and pathobiological activity, and targeted study of normally functioning and pathological native and substitute human valves. Collectively, these developments have facilitated a growing understanding of how shortand long-term biomechanical valve function at the organ level relates to tissue and cell structure and normal valve function, elucidated the pathological anatomy and mechanisms of valvular dysfunction, fostered improvements in tissue heart valve substitutes and surgical repairs, and informed innovative approaches to heart valve tissue engineering and regeneration. [1][2][3][4] In this communication, we highlight key recent insights into heart valve function and dysfunction and their implications for the prevention, diagnosis, and treatment of clinical heart valve disease, currently and in the future. The heart valves are tissue structures whose motions are driven by mechanical forces exerted by the surrounding blood and heart. The ability of the valves to permit unobstructed forward flow depends on the mobility, pliability, and structural integrity of their leaflets (in the TV and MV) and cusps (in the PV and AV).The individual AV cusps attach to the aortic wall in a crescentic (or semilunar) fashion, ascending to the commissures (where adjacent cusps come together at the aorta) and descending to the basal attachment of each cusp to the aortic wall. Behind the cusps are dilated pockets in the aortic root, called sinuses of Valsalva, which bulge with each ejection of blood. The AV cusps and their respective sinuses are named for their relationship to the coronary artery ostia that arise from them, normally a left, a right, and a noncoronary (cusp and associated sinus). In the middle of the free edge of each cusp on the ventricular surface is a ...

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

“…This process is likely mediated by elevated LV AngII signaling, which in turn promotes valvular in situ leptin synthesis. Leaflet hyperplasia is an early event preceding subsequent macrophage infiltration and cellular mineralization interacting with valve biomechanics,46 constituting a chain of events leading to advanced AVS in humans (Figure 8). Hyperplastic lesions in mouse aortic valves in both models exhibited increased expression of TGF‐β1.…”

The pathology and pathobiology of bicuspid aortic valve: State of the art and novel research perspectives

“…In CAVD, the increased mechanical stress on resident VICs induced by aging‐related valvular remodelling, inflammation and other mechanical and biochemical processes could play an important role in early cell injury (apoptosis or necrosis) and osteogenic differentiation of VICs 12, 13. Apoptosis/necrosis‐enabled dystrophic calcification mechanisms, in which cell injury is an important and early event, are exemplified by the failure of glutaraldehyde‐treated bioprosthetic substitute heart valves, in which calcification is initiated primarily within residual, non‐viable porcine aortic valve or bovine pericardial cells 14. Mineral found in CAVD is mostly hydroxyapatite of calcium (HAC), similar to bone mineral, which can be deposited by an apoptosis‐mediated process or by osteogenic activity 15, 16.…”

“…The normal aortic valve is avascular and the formation of neovessels participates in the development of CAVD 14. To this end, stenotic BAVs demonstrate increased remodelling, neovascularisation and inflammatory infiltration compared to TAV, even when accounting for other risk factors for CAVD 33, 34.…”

Tissue engineering on matrix: future of autologous tissue replacement

“…Besides being biodegradable, biocompatible, and reproducible, the scaffold material should also display a cell-favorable surface chemistry and match the bio-mechanical properties of the native heart valve tissue [12]. In addition, the rate of matrix degradation should be controllable and commensurate with the rate of novel tissue formation in order to provide a sufficient but reducing mechanical stability of the construct over time [1,62]. Several synthetic biodegradable polymers have been investigated as potential starter matrices for heart valve tissue engineering that vary in their manufacturing possibilities and degradation rates (Table 1).…”

“…1). Native heart valves are composed of living, dynamic tissue capable of continuous remodeling to adapt to the constantly alternating hemodynamic environment [1]. None of the currently available valvular replacements are capable of fully restoring the native function due to insufficient adaptive capacity.…”