L25-27 - vascular bio

• innermost blood vessel layer, faces lumen • four layers from inner to outer: 1. endothelium - simple squamous 2. basal lamina 3. subendothelial CT - ECM + cells to synth ECM *sometimes smooth muscles (path) 4. internal elastic lamina - fenestrated for gas/nutrient exchange + elastin (NOT elastic fibers) • elastin

• middle blood vessel layer • smooth muscle + external elastic lamina - fenestrated for vasa vasorum feeds it • no nervi vasorum • elastin, elastic fibers (BOTH!), ibronectin, fibrillin-1, reticular fibers, proteoglycans

• CT layer, contains nerves and blood vessels • type 1 collagen, elastic fibers, fibroblasts • vasa vasorum - BV go through ext elastic lamina fenestrations to media • nervi vasorum - nerves to BV, sympathetic, “fluorescent light halo” - gap junctions

• required vessels >1mm • contributes to angiogenesis and inflammation in atherosclerosis • syphilis = inflamed ascending aorta –> endarteritis and periarteritis –> obliterated vasa vasorum –> focal necrosis/scarring media –> degeneration elastic lamellae –> tree bark appearance to intima

• simple squamous • elongated in direction of blood flow • connected by cellular junctions • have myoendothelial junction to communicate with smooth m. through fenestrations in internal elastic lamina for vasodilation • many pinocytotic vesicles • some apical microvilli • contain Weibel-Palade bodies

• arteries - nerve endings found in adventitia, not media • veins - nerve ends found in both, less density than arteries • mainly sympathetic

shear stress by blood flow => hyperpolarization of endothelial cell => through gap junctions to vascular smooth m. => vasodilation

• promote/inhibit blood coagulation (protein S) • make prostacyclin = vasodilator • modulate smooth muscle activity (endothelin-1 is a vasoconstrictor and NO is a vasodilator) • regulate inflammatory cell traffic • transport (pinocytotic vesicles) • regulate angiogenesis • movement of inflammatory cells from lumen to tissue (selectin = adhesion molecule)

• contain Von Willebrad factor (coag VIII) • tissue plasminogen activator • interleukin 8 • P-selectin (allows leuks to connect to endothelial cells memb)

• arteries have lots of smooth muscle vs. veins have lots of CT • capillaries are just endothelium and BL • arteries have prominent internal elastic membrane

• characteristic alternating layers of smooth muscle and fenestrated elastic lamellae (NO elastic fibers) • vasa vasorum down to middle of tunica media • fibroblasts in adventitia only usually • aorta, brachiocephalic trunk

• elastic fibers instead of just elastin which disrupts the structural integrity • microfibrils cause disarray, leading to degeneration of elastic components and lakes of mucopolysaccharides (GAG deposits)

• incr. # elastic lamellae in media with age (smooth m. incr. also) • subendothelial compartment thickens + moderate intimal fibrosis (normal) • minor elastic lamellae fragmentation (normal) • some picketing in intima

• medium artery • lots of smooth muscle in the tunica media (brown/yellow, dark nuclei) • less elastic elements • prominent internal and external elastic membranes (dark) • elastic fibers in adventitia

• fragmentation • intimal hyperplasia (fibrosis) • duplication of internal elastic lamina • aneurysm - circle of Willis

1

• continuous - specific transport without leakage - found in CNS, lungs, muscle, adipose, exocrine - tight junctions, no pores - numerous pinocytotic vesicles - well developed basal lamina • fenestrated - found in kidneys, intestines, endocrine - fenestrations in endothelial wall for rapid movement of material between lumen and EC - diaphragms close pores (no diaphragms in glomerulus) - continuous BL • sinusoid - found in red bone marrow, spleen, adrenal cortex, liver - very rapid exchange - larger diameter, huge pores (larger than fenestrations) - absent BL

larger lumen, thinner walls, no IEL or EEL, less smooth m. and elastic elements

• pericytic - smallest venules surrounded by pericytes, in microcirculation • muscular - larger venules, with smooth muscle in tunica media

• mesenchymal cells • contractile • can transform into smooth m. and fibroblasts • contribute to scar tissue in CNS, etc.

vasculogenesis = de novo blood vessel formation angiogenesis = BV growth from existing endothelial cell-derived channels arteriogenesis = formation of arteries, arteriole/collateral vessel remodeling neovascularization = umbrella term for vasculo-, angio- and arterio- genesis remodeling = vascular changes due to change in the environment

• from endothelial precursor cells (EPCs) • from pre-existing vessels *tumor angiogenesis uses both of these

vasculogenesis = new BV formation from EPCs used to: • replace lost endothelial cells • re-endothelization of vascular implants • neovascularization of ischemic organs, wounds, and tumors steps: • stimuli • EPCs leave bone marrow • EPCs enter vasculogenesis site • BV form

angiogenesis = new BV from pre-existing BV • vasodilation (NO) + increased permeability (VEGF) • degradation of BL (metalloproteases) + loss of cell-to-cell contact/junctions (plasminogen activator) • those endothelial cells migrate and proliferate (proangiogenic factors -VEGF/angiopoietin 2 and FGF2) • endothelial cells mature into endothelial capillary tube • elaborate BL (TGF-B) + recruit periendothelial cells (pericytes by Ang 1 with Tie2 and smooth m. by PDGR) *also Ang 2 blocks stabilizing activity of Ang 1 so remodeling can occur