Aquaporin-1 shifts the critical transmural pressure to compress the aortic intima and change transmural flow: theory and implications.
Am J Physiol Heart Circ Physiol
; 309(11): H1974-86, 2015 Dec 01.
Article
in En
| MEDLINE
| ID: mdl-26342066
ABSTRACT
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 â¼43 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Aorta
/
Body Water
/
Tunica Intima
/
Mechanotransduction, Cellular
/
Atherosclerosis
/
Aquaporin 1
/
Arterial Pressure
/
Models, Cardiovascular
Type of study:
Prognostic_studies
/
Qualitative_research
Limits:
Animals
/
Humans
Language:
En
Journal:
Am J Physiol Heart Circ Physiol
Journal subject:
CARDIOLOGIA
/
FISIOLOGIA
Year:
2015
Type:
Article