Mechanotransduction and Vascular Resistance

International audienceMechanotransduction is the process by which any cell transduces (converts) a mechanical signal into chemical cues. The vessel wall is permanently sheared by the moving blood particles as well as stretched and compressed by the pressure applied by the blood. Multiple types of mechanical stress fields are associated with flow patterns and unsteadiness.Mechanosensing occurs locally at the plasma membrane. It relies on detection of local changes in protein conformation that lead to ion channel opening, protein unfolding, modified enzyme kinetics, and variations in molecular interactions following exposure of buried binding site or, conversely, hiding them.Mechanotransduction initiates several signaling pathways. Multiple mediators include: At the cell surface, G-protein-coupled and protein tyrosine kinase receptors, ion channels, enzymes, adhesion molecules, and specialized plasmalemmal nanodomains At the cell cortex, the cortical actin network that regulates the cell-surface mechanics and signaling adaptors and effectors (e.g., small monomeric guanosine triphosphatases and heterotrimeric guanine nucleotide-binding proteins, kinases, phosphatases, and ubiquitins, among others) In the cytosol, enzymes, scaffolds, carriers such as endosomes, calcium concentration, and transcription factors In the nucleus, nuclear pore carriers, enzymes, and the transcriptional and translational machineryMechanotransduction by vascular cells regulate the contraction–relaxation state of vascular smooth myocytes, thereby regulating locally and quickly the size of the vascular lumen, that is, the local vascular resistance to blood flow. Once experiencing an unusual mechanical stress, vascular smooth myocytes react by contracting or relaxing according to the magnitude of the mechanical stress, the value of which rises above or falls below the range in which it fluctuates in normal conditions. Moreover, they receive chemical and electrochemical signals from endotheliocytes, themselves sensing the wall shear stress at their wetted (luminal) surface.Mechanotransduction thus regulates locally blood flow more rapidly than the endocrine regulation by remote tissues and even than that of the nervous system, which transmits signals very rapidly via afferent nerves and, after processing in the centers of the spinal cord and brain, efferent nerves

The primary vascular dysregulation syndrome: implications for eye diseases

Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood-brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide recommendations on how to effectively promote the field in order to create innovative diagnostic tools to predict the pathology and develop more efficient treatment approaches tailored to the person