Aquaporin-1 shifts the critical transmural pressure to compress the aortic intima and change transmural flow: theory and implications.
Transmural-pressure (ΔP)-driven plasma advection carries macromolecules into the vessel wall, the earliest prelesion atherosclerotic event. The wall's hydraulic conductivity, LP, the water flux-to-ΔP ratio, is high at low pressures, rapidly decreases, and remains flat to high pressures (Baldwin AL, Wilson LM. Am J Physiol Heart Circ Physiol 264: H26-H32, 1993; Nguyen T, Toussaint, Xue JD, Raval Y, Cancel CB, Russell LM, Shou S, Sedes Y, Sun O, Yakobov Y, Tarbell JM, Jan KM, Rumschitzki DS. Am J Physiol Heart Circ Physiol 308: H1051-H1064, 2015; Tedgui A, Lever MJ. Am J Physiol Heart Circ Physiol. 247: H784-H791, 1984. Shou Y, Jan KM, Rumschitzki DS. Am J Physiol Heart Circ Physiol 291: H2758-H2771, 2006) due to pressure-induced subendothelial intima (SI) compression that causes endothelial cells to partially block internal elastic laminar fenestrae. Nguyen et al. showed that rat and bovine aortic endothelial cells express the membrane protein aquaporin-1 (AQP1) and transmural water transport is both transcellular and paracellular. They found that LP lowering by AQP1 blocking was perplexingly ΔP dependent. We hypothesize that AQP1 blocking lowers average SI pressure; therefore, a lower ΔP achieves the critical force/area on the endothelium to partially block fenestrae. To test this hypothesis, we improve the approximate model of Huang et al. (Huang Y, Rumschitzki D, Chien S, Weinbaum SS. Am J Physiol Heart Circ Physiol 272: H2023-H2039, 1997) and extend it by including transcellular AQP1 water flow. Results confirm the observation by Nguyen et al.: wall LP and water transport decrease with AQP1 disabling. The model predicts 1) low-pressure LP experiments correctly; 2) AQP1s contribute 30-40% to both the phenomenological endothelial + SI and intrinsic endothelial LP; 3) the force on the endothelium for partial SI decompression with functioning AQP1s at 60 mmHg equals that on the endothelium at ∼43 mmHg with inactive AQP1s; and 4) increasing endothelial AQP1 expression increases wall LP and shifts the ΔP regime where LP drops to significantly higher ΔP than in Huang et al. Thus AQP1 upregulation (elevated wall LP) might dilute and slow low-density lipoprotein binding to SI extracellular matrix, which may be beneficial for early atherogenesis.
Department of Chemical Engineering, City College of the City University of New York, New York; and.
Shripad
S
Joshi
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York.
Kung-Ming
KM
Jan
Department of Chemical Engineering, City College of the City University of New York, New York; and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York david@che.ccny.cuny.edu.
David S
DS
Rumschitzki
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000503:physiopathology; D051398:Aquaporin 1 / Q000378:metabolism*; D062186:Arterial Pressure; D050197:Atherosclerosis / Q000378:metabolism* / Q000503:physiopathology; D001783:Blood Flow Velocity; D001834:Body Water / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D040542:Mechanotransduction, Cellular; D008955:Models, Cardiovascular; D009716:Numerical Analysis, Computer-Assisted; D012039:Regional Blood Flow; D015398:Signal Transduction; D017539:Tunica Intima / Q000378:metabolism* / Q000503:physiopathology
D051398:Aquaporin 1
aquaporin-1; atherosclerosis; transcellular transport; wall hydraulic conductivity