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Early Atherosclerotic Changes in Coronary Arteries are Associated with Endothelium Shear Stress Contraction/Expansion Variability.

ABSTRACT: Although unphysiological wall shear stress (WSS) has become the consensus hemodynamic mechanism for coronary atherosclerosis, the complex biomechanical stimulus affecting atherosclerosis evolution is still undetermined. This has motivated the interest on the contraction/expansion action exerted by WSS on the endothelium, obtained through the WSS topological skeleton analysis. This study tests the ability of this WSS feature, alone or combined with WSS magnitude, to predict coronary wall thickness (WT) longitudinal changes. Nine coronary arteries of hypercholesterolemic minipigs underwent imaging with local WT measurement at three time points: baseline (T1), after 5.6 ± 0.9 (T2), and 7.6 ± 2.5 (T3) months. Individualized computational hemodynamic simulations were performed at T1 and T2. The variability of the WSS contraction/expansion action along the cardiac cycle was quantified using the WSS topological shear variation index (TSVI). Alone or combined, high TSVI and low WSS significantly co-localized with high WT at the same time points and were significant predictors of thickening at later time points. TSVI and WSS magnitude values in a physiological range appeared to play an atheroprotective role. Both the variability of the WSS contraction/expansion action and WSS magnitude, accounting for different hemodynamic effects on the endothelium, (1) are linked to WT changes and (2) concur to identify WSS features leading to coronary atherosclerosis.

SUBMITTER: Mazzi V

PROVIDER: S-EPMC8455396 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and purposeThromboxane A(2) and endothelial dysfunction are implicated in the development of pulmonary hypertension. The receptor-transduction pathway for U46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F(2 alpha))-induced contraction was examined in endothelium-intact (E+) and denuded (E-) rat pulmonary artery rings.Experimental approachArtery rings were mounted on a wire myograph under a tension of 7-7.5 mN at 37 degrees C and gassed with 95% O(2)/5% CO(2). Isometric recording was made by using Powerlab data collection and Chart 5 software.Key resultsBoth E+ and E- contractile responses were sensitive to Rho-kinase inhibition and the chloride channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)benzoic acid]. The E+ response was sensitive to the store-operated calcium channel blockers SKF-96365 {1-[B-[3-(4-methoxyphenyl)propoxy]-4-methoxy-phenethyl]-1H-imidazole hydrochloride} and 2-APB (2-amino ethoxy diphenylborate) (75-100 micromol x L(-1)). The E- response was sensitive to 2-APB (10-30 micromol x L(-1)), a putative IP(3) receptor antagonist, and the calcium and chloride channel blockers nifedipine, DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) and niflumic acid but was insensitive to SKF-96365. Inhibiting K(V) with 4-AP in E+ rings exposed a contraction sensitive to nifedipine, DIDS and niflumic acid, whereas inhibiting BK(Ca) exposed a contraction sensitive to mibefradil, DIDS and niflumic acid. This indicates that removal of the endothelium allows the TP receptor to inhibit K(V), which may involve coupling to phospholipase C, because inhibition of phospholipase C with U73122 (1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-y]amino]hexyl]- 1H-pyrrole-2,5-dione) switched the E- pathway to the E+ pathway.Conclusions and implicationsThe results from this study indicate that distinct transduction pathways can be employed by the TP receptor to produce contraction and that the endothelium is able to influence the coupling of the TP receptor.

Project description:BACKGROUND:Enhanced External Counterpulsation (EECP) can chronically relieve ischemic chest pain and improve the prognosis of coronary heart disease (CHD). Despite its role in mitigating heart complications, EECP and the mechanisms behind its therapeutic nature, such as its effects on blood flow hemodynamics, are still not fully understood. This study aims to elucidate the effect of EECP on significant hemodynamic parameters in the coronary arterial tree. METHODS:A finite volume method was used in conjunction with the inlet pressure wave (surrogated by the measured aortic pressure) before and during EECP and outlet flow resistance, assuming the blood as newtonian fluid. The time-average wall shear stress (TAWSS) and oscillatory shear index (OSI) were determined from the flow field. RESULTS:Regardless of the degree of vascular stenosis, hemodynamic conditions and flow patterns could be improved during EECP. In comparison with the original tree, the tree with a severe stenosis (75% area stenosis) demonstrated more significant improvement in hemodynamic conditions and flow patterns during EECP, with surface area ratio of TAWSS risk area (SAR-TAWSS) reduced from 12.3% to 6.7% (vs. SAR-TAWSS reduced from 7.2% to 5.6% in the original tree) and surface area ratio of OSI risk area (SAR-OSI) reduced from 6.8% to 2.5% (vs. SAR-OSI of both 0% before and during EECP in the original tree because of mild stenosis). Moreover, it was also shown that small ratio of diastolic pressure (D) and systolic pressure (S) (D/S) could only improve the hemodynamic condition mildly. The SAR-TAWSS reduction ratio significantly increased as D/S became larger. CONCLUSIONS:A key finding of the study was that the improvement of hemodynamic conditions along the LMCA trees during EECP became more significant with the increase of D/S and the severity degree of stenoses at the bifurcation site. These findings have important implications on EECP as adjuvant therapy before or after percutaneous coronary intervention (PCI) in patients with diffuse atherosclerosis.

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Early Atherosclerotic Changes in Coronary Arteries are Associated with Endothelium Shear Stress Contraction/Expansion Variability.

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