Changes in biomechanical properties of the coronary artery wall contribute to maintained contractile responses to endothelin-1 in atherosclerosis.
OBJECTIVE
Our aim was to determine whether alterations in biomechanical properties of human diseased compared to normal coronary artery contribute to changes in artery responsiveness to endothelin-1 in atherosclerosis.


METHODS
Concentration-response curves were constructed to endothelin-1 in normal and diseased coronary artery. The passive mechanical properties of arteries were determined using tensile ring tests from which finite element models of passive mechanical properties of both groups were created. Finite element modelling of artery endothelin-1 responses was then performed.


RESULTS
Maximum responses to endothelin-1 were significantly attenuated in diseased (27±3 mN, n=55) compared to normal (38±2 mN, n=68) artery, although this remained over 70% of control. There was no difference in potency (pD2 control=8.03±0.06; pD2 diseased=7.98±0.06). Finite element modelling of tensile ring tests resulted in hyperelastic shear modulus μ=2004±410 Pa and hardening exponent α=22.8±2.2 for normal wall and μ=2464±1075 Pa and α=38.3±6.7 for plaque tissue and distensibility of diseased vessels was decreased. Finite element modelling of active properties of both groups resulted in higher muscle contractile strain (represented by thermal reactivity) of the atherosclerotic artery model than the normal artery model. The models suggest that a change in muscle response to endothelin-1 occurs in atherosclerotic artery to increase its distensibility towards that seen in normal artery.


CONCLUSIONS
Our data suggest that an adaptation occurs in medial smooth muscle of atherosclerotic coronary artery to maintain distensibility of the vessel wall in the presence of endothelin-1. This may contribute to the vasospastic effect of locally increased endothelin-1 production that is reported in this condition.
Department of Engineering, University of Cambridge, UK.
Chen Yen
CY
Ooi
Department of Engineering, University of Cambridge, UK.
Michael P F
MP
Sutcliffe
Clinical Pharmacology Unit, University of Cambridge, UK.
Anthony P
AP
Davenport
Clinical Pharmacology Unit, University of Cambridge, UK. Electronic address: jjm1003@medschl.cam.ac.uk.
Janet J
JJ
Maguire
D050197:Atherosclerosis / Q000503:physiopathology*; D001696:Biomechanical Phenomena / Q000187:drug effects; D003331:Coronary Vessels / Q000503:physiopathology*; D019332:Endothelin-1 / Q000494:pharmacology*; D020342:Finite Element Analysis; D006801:Humans; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects*
D019332:Endothelin-1
Arterial stiffness; Atherosclerosis; Biomechanical properties; Endothelin-1; Human coronary artery; Vasoconstriction