The Calcium Signaling Mechanisms in Arterial Smooth Muscle and Endothelial Cells

Reactive Oxygen Species and Endothelial Ca2+ Signaling: Brothers in Arms or Partners in Crime?

“…TRPC3 is a DAG-sensitive channel that presents a P Ca /P Na of 1.62 and mediates extracellular Ca 2+ entry upon PLC recruitment by G q/11 PCRs and TKRs [ 7 , 206 ]. TRPC3-dependent increase in endothelial [Ca 2+ ] i controls proliferation, migration, tube formation, barrier permeability, and generation of chemical (e.g., NO) and electrical (i.e., EDH) vasorelaxing signals [ 15 , 106 , 204 ].…”

“…TRPV4 is gated by a multitude of cues, including a moderate increase in temperature (>27 °C), pulsatile stretch, laminar shear stress, hypotonic cell swelling, arachidonic acid, EETs, and anandamide [ 217 , 218 ]. Furthermore, the endothelial TRPV4 is finely tuned by G q/11 PCRs/PLC signaling, as extensively reviewed in [ 7 , 25 , 217 ]. TRPV4 was found to support H 2 O 2 -induced increase in [Ca 2+ ] i in both mouse and human mouse pulmonary microvascular endothelial cells ( Table 2 ) [ 219 ].…”

“…TRPM2 is a nonselective cation channel that displays a linear current-to-voltage relationship with a reversal potential (E rev ) of ~0 mV and a P Ca /P Na of ~0.3-0.9 [ 227 ]. TRPM2-mediated extracellular Ca 2+ entry regulates a variety of endothelial functions, ranging from the control of vascular permeability and blood pressure to angiogenesis [ 5 , 7 , 228 ]. TRPM2 can be indirectly activated by extracellular H 2 O 2 that accumulates during tissue inflammation and damage.…”

“…TRPM4 is a Ca 2+ -activated, Ca 2+ -impermeable nonselective cation channel that presents a P Ca /P Na of 0.09 [ 7 ] and control endothelial cell permeability and sprouting angiogenesis [ 5 ]. At the negative resting membrane potential (V M ) of vascular endothelial cells [ 106 ], extracellular Na + entry through TRPM4 depolarizes V M to dampen the driving force sustaining Ca 2+ influx into the cytosol and thereby prevents the cytotoxic Ca 2+ overload [ 5 ].…”

“…Therefore, peripheral vasculature is endowed with multiple progenitor cell niches that release on demand, e.g., upon an ischemic insult or a traumatic injury, endothelial colony forming cells (ECFCs) to replace damaged endothelial cells [ 4 ]. An increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) is the most versatile signaling pathway whereby either a subtle or gross change in extracellular microenvironment may instruct endothelial cells and circulating ECFCs to perform a specific task to maintain cardiovascular homeostasis [ 1 , 2 , 5 , 6 , 7 , 8 , 9 ]. Distinct spatiotemporal endothelial Ca 2+ signals tightly regulate different functions such as nitric oxide (NO) release [ 10 , 11 , 12 ] and endothelium-dependent hyperpolarization (EDH) [ 13 ], vascular permeability [ 14 , 15 ] and repair [ 16 , 17 ], platelet aggregation and blood coagulation [ 18 , 19 ], leukocyte/lymphocyte infiltration [ 20 , 21 , 22 , 23 ], neurovascular coupling [ 24 , 25 ], wound healing [ 16 , 17 ], angiogenesis [ 5 , 26 ], and vasculogenesis [ 27 ].…”