Regulation of vascular tone is a complex process that remains poorly understood. Here, we present our recent efforts for the development of physiologically realistic models of arterial segments for the analysis of vasoreactivity in health and disease. Multiscale modeling integrates intracellular and cell membrane components into whole-cell models of calcium and membrane potential dynamics. Single-cell models of vascular cells are combined into a multicellular model of the vascular wall, and vessel wall biomechanics are integrated with calcium dynamics in the smooth muscle layer. At each scale, continuum models using finite element method can account for spatial heterogeneity in calcium signaling and for nonuniform deformations of a vessel segment. The outlined approach can be used to investigate cellular mechanisms underlying altered vasoreactivity in hypertension.
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http://dx.doi.org/10.1109/TBME.2011.2162513 | DOI Listing |
Vascul Pharmacol
January 2025
Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, 10043 Orbassano, Italy. Electronic address:
The appropriate regulation of peripheral vascular tone is crucial for maintaining tissue perfusion. Myoendothelial junctions (MEJs), specialized connections between endothelial cells and vascular smooth muscle cells, are primarily located in peripheral resistance vessels. Therefore, these junctions, with their key membrane proteins, play a pivotal role in the physiological control of relaxation-contraction coupling in resistance arterioles, mainly mediated through endothelium-derived hyperpolarization (EDH).
View Article and Find Full Text PDFPhytomedicine
December 2024
Univ Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Azinhaga de S. Comba, Coimbra 3000-548, Portugal; Univ Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; Clinical Academic Centre of Coimbra (CACC), Coimbra, Portugal.
Background: Pulmonary Arterial Hypertension (PAH) is characterized by pulmonary vascular remodelling, often associated with disruption of BMPR2/Smad1/5 and BMPR2/PPAR-γ signalling pathways that ultimately lead to right ventricle failure. Disruption of intercellular junctions and communication and a pro-angiogenic environment are also characteristic features of PAH. Although, current therapies improve pulmonary vascular tone, they fail to tackle other key pathological features that could prevent disease progression.
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
February 2025
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
The media-lumen diameter ratio of small arteries is increased in hypertension, diabetes and obesity. It is likely that both shear stress on the endothelial cells, transmural pressure and smooth muscle cell tone are important for the altered vascular structure. However, the precise interaction and importance of these factors are incompletely understood.
View Article and Find Full Text PDFActa Physiol (Oxf)
February 2025
Cardiovascular Health Across the Life Span, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Preserving the balance of metabolic processes in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), is crucial for optimal vascular function and integrity. ECs are metabolically active and depend on aerobic glycolysis to efficiently produce energy for their essential functions, which include regulating vascular tone. Impaired EC metabolism is linked to endothelial damage, increased permeability and inflammation.
View Article and Find Full Text PDFJ Hypertens
December 2024
Institute for Fetology, The First Affiliated Hospital of Soochow University, Jiangsu.
Background: Paternal preconception alcohol exposure affects fetal development; however, it is largely unknown about the influences on offspring vasculature and mechanisms.
Methods: Offspring born form paternal rats treated with alcohol or water before pregnant was raised until 3 months of age. Vessel tone of mesenteric arteries was detected using myograph system; whole-cell calcium channel current in smooth muscle cells was tested using patch-clamp; molecule expressions were detected with real-time PCR, western blotting, and Dihydroethidium (DHE); DNA methylations were determined using targeted bisulfate sequencing assay.
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