Embryology of the Aortic Valve and Second Messenger Pathways

Gloria Teresa^*
*Correspondence: Gloria Teresa, Department of Cardiology, University of Oakland, 318 Meadow Brook Rd, Rochester, MI 48309, USA, Email:

Introduction

The aortic valve, a critical component of the heart, undergoes complex embryological development. The heart develops from the primary heart field, which gives rise to the linear heart tube. The second heart field contributes to the elongation and looping of the heart tube, and the Outflow Tract (OFT) forms the precursor of the aortic valve. During early development, endothelial cells within the OFT form endocardial cushions. These cushions undergo remodelling, resulting in the formation of semilunar leaflets, including those of the aortic valve. Distinctive molecular signaling pathways, such as Notch, Wnt, and TGF-β, play pivotal roles in the differentiation and patterning of the valve leaflets. Genetic mutations or perturbations in these pathways can lead to congenital valve malformations. Mechanobiology refers to the interplay between mechanical forces and biological responses in living organisms. In the context of the aortic valve, mechanobiology is crucial for maintaining tissue homeostasis and responding to hemodynamic forces. The valve experiences various mechanical stresses, including tensile, compressive, and shear forces, which influence its cellular and Extracellular Matrix (ECM) properties [1].

Description

Valve Interstitial Cells (VICs) are the predominant cell type in the aortic valve, responsible for maintaining ECM integrity and responding to mechanical cues. VICs exhibit phenotypic plasticity, transitioning between quiescent fibroblast-like states and activated myofibroblast-like states in response to mechanical and biochemical stimuli. Dysregulation of mechanotransduction pathways, such as focal adhesion kinase and Rho GTPases, can contribute to valve pathologies, including calcific aortic valve disease [2].

Second messenger pathways are signaling cascades that transmit extracellular signals to intracellular effectors, regulating various cellular processes. In the aortic valve, second messenger pathways mediate responses to mechanical forces, growth factors, and inflammatory cytokines, modulating valve homeostasis and pathology. One key second messenger pathway in the aortic valve is the cyclic adenosine monophosphate pathway. CAMP is generated by adenylyl cyclases in response to signaling through G proteincoupled receptors. In VICs, cAMP signaling regulates ECM synthesis, cell proliferation, and contractility through downstream effectors such as protein kinase A and exchange protein directly activated by cAMP [3].

Another important second messenger pathway is the Phosphoinositide 3-Kinase (PI3K)/Akt pathway. Activation of PI3K by growth factors or mechanical forces leads to the generation of Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which recruits Akt to the plasma membrane. Akt phosphorylates various targets involved in cell survival, proliferation, and metabolism. In the aortic valve, PI3K/Akt signaling regulates VIC phenotype and ECM remodelling in response to mechanical stretch and growth factors. Furthermore, calcium signaling plays a critical role in aortic valve physiology and pathology. Intracellular calcium levels are tightly regulated by calcium channels, pumps, and exchangers. Calcium signaling modulates VIC contractility, ECM synthesis, and valve calcification. Dysregulation of calcium handling can promote valve stiffening and calcification, contributing to aortic stenosis [4,5].

Conclusion

The embryology, mechanobiology, and second messenger pathways of the aortic valve are intricately interconnected, governing its development, homeostasis, and response to pathological stimuli. Understanding these fundamental aspects is crucial for elucidating the etiology of valve diseases and developing targeted therapeutic interventions to alleviate valve pathologies and improve patient outcomes. Further research into these areas promises to uncover novel insights into aortic valve biology and pathology, with potential implications for clinical practice.

Acknowledgement

None.

Conflict of Interest

None.

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