Cell-cell communication in the resistance vasculature: the past, present, and future

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...

Vascular resistance is a critical concept in understanding blood flow dynamics in the circulatory system. It refers to the resistance that blood encounters as it flows through the blood vessels. This resistance is a key factor in determining blood pressure and cardiac workload.
The primary determinants of vascular resistance are vessel diameter, blood viscosity, and vessel length. Among these, vessel diameter plays the most significant role due to the fourth power relationship described by...

The vascular system comprises an extensive network of arteries, capillaries, and veins. The vascular system can be broadly divided into the blood and lymphatic systems. Typically, blood vessels can be categorized into three histological regions: tunica intima, tunica media, and tunica adventitia. The tunica intima consists of a single layer of endothelial cells attached to the basal lamina. Underlying the basal lamina is a connective tissue layer and an elastic lamina that gives stability and...

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...

The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...

Paracrine signaling allows cells to communicate with their immediate neighbors via secretion of signaling molecules. Such a signal can only trigger a response in nearby target cells because the signal molecules degrade quickly or are inactivated if not taken up. Prominent examples of paracrine signaling include nitric oxide signaling in blood vessels, synaptic signaling of neurons, the blood clotting system, tissue repair/wound healing, and local allergic skin reactions. Nitric oxide as a...