Dioscorea deltoidei (Dioscoreaceae) leaf extract exerts anti-atherosclerotic effect in rats via down-regulation of phosphorylated JAK/STAT

Purpose: To investigate the effect of leaf extract of Dioscorea deltoidea (Dioscoreaceae) leaf (DDE) on atherosclerosis-induced aorta wall damage in a rat model, and the underlying mechanism of action.Methods: Rats were fed high-fat diet containing vitamin D2 for 16 weeks to induce atherosclerosis. Histopathological changes in the aorta were examined using hematoxylin and eosin (H & E) staining, while ELISA kits were used to measure cytokine levels.Results: Treatment with DDE significantly (p < 0.05) alleviated atherosclerosis-induced increase in mean lesion area in the rat aorta. The mean lesion area in atherosclerotic rats was decreased to 51.5, 21.2 and 2.3 mm2, on treatment with DDE at doses of 2.5, 5 and 10 mg/kg, respectively. Furthermore, DDE significantly suppressed atherosclerosis-induced elevation in IL-1β and IL-6 levels in the rat aorta (p < 0.05). The levels of MCP-1 and TNF-α decreased in the artherosclerotic rats on treatment with DDE. In DDE-treated rats, the atherosclerosis-induced increase in the levels of Ang II, AT1, AT2, p-STAT3, p-p65 and p-p38 were significantly decreased, relative to the model group (p < 0.05). However, DDE treatment did not alter the levels of total STAT3, p65 and p38 in the rat aorta tissues.Conclusion: These results indicate that DDE inhibits inflammatory response and atherosclerosisinduced damage to aorta wall. Moreover, RAAS expression, inflammatory cytokines and JAK/STAT signalling pathway were down-regulated in atherosclerotic rats on treatment with DDE. Thus, DDE may be a potential source of drug for the management of atherosclerosis.

Distinct Chemical Changes in Abdominal but Not in Thoracic Aorta upon Atherosclerosis Studied Using Fiber Optic Raman Spectroscopy

Fiber optic Raman spectroscopy and Raman microscopy were used to investigate alterations in the aorta wall and the surrounding perivascular adipose tissue (PVAT) in the murine model of atherosclerosis (Apoe-/-/Ldlr-/- mice). Both abdominal and thoracic parts of the aorta were studied to account for the heterogenic chemical composition of aorta and its localization-dependent response in progression of atherosclerosis. The average Raman spectra obtained for both parts of aorta cross sections revealed that the chemical composition of intima-media layers along aorta remains relatively homogeneous while the lipid content in the adventitia layer markedly increases with decreasing distance to PVAT. Moreover, our results demonstrate that the increase of the lipid to protein ratio in the aorta wall correlates directly with the increased unsaturation level of lipids in PVAT and these changes occur only in the abdominal, but not in thoracic, aorta. In summary, distinct pathophysiological response in the aortic vascular wall could be uncovered by fiber optic Raman spectroscopy based on simple parameters detecting chemical contents of lipids in PVAT.

P1382 Evidence for longitudinal aorta strain relationship with noninvasive left ventricular myocardial work: another component for the ventricular-aorta coupling?

The force required to produce longitudinal strain of the aorta represents an often overlooked mechanical load imposed on the left ventricle (LV). 2D speckle tracking strain analysis (2D-SpTa) may be applied on aorta wall in order to evaluate regional longitudinal strain (AoSTR). A noninvasive method for measuring LV myocardial work (MW) has been recently proposed, based on 2D-SpTa combined with estimated pressure curve. Aim of the study was to assess the relationship of both LV conventional functional indices and the new MW ones with the aorta function estimated by AoSRT in normals and to interrogate the potential effect of aging. Methods Fifty four normals, 24 males (M) and 30 females(F), age: 52 ± 13 (25-75 years), were selectively studied, provided that they had an efficient image quality to apply both AFI analysis for MW estimation and ascending aorta interrogation for AoLSTR (EchoPac GE) . LAoLSTR was measured in the posterior aorta wall (apical long axis view). Aortic wall borders were traced longitudinally adjusting width using 4 points of interest. The first point was put at the sinotubular junction and approximately 3-4 cm of the ascending aorta were analyzed. 2D-SpTa divided the regions of interest into proximal, middle and distal segments and the respective peak LAoSTR were considered. The following indexes of MW were estimated: GWI (global work index = total work from mitral valve closure to mitral valve opening), GCW (global constructive work = total work contributing to pump function, namely due to shortening during isovolumic contraction and ejection and lengthening during isovolumic relaxation), GWW (global wasted work = elongation during isovolumic contraction/ejection and shortening during isovolumic relaxation), GWE (global work efficiency = fraction of GCW/[GCW + GWW]). AFI derived LV strain (LVGS), biplane LV ejection fraction and stroke volume (SV) were also calculated. Results LAoSTR in any wall position was not affected by age. LAoLSTR of the proximal segment was related to both EF and LVGS (r = 0.31, p = 0.03 and r=-0.28 p = 0.05, respectively). Middle and distal LAoSTR were not related to either EF or LVGS. SV was not related to any of LAoSTR. LAoSTR of the proximal segment was related to both GWI and GCW ( r = 0.34 p = 0.016 and r = 0,31 p = 0.03 respectively). LAoSTR of the middle and distal segments were not related with any LV MW parameters. Conclusion Longitudinal aorta strain evaluation by 2D-SpTa is feasible and it is related with functional performance of the LV estimated by either conventional or MW indices based on 2D-SpTa. Moreover , the longitudinal performance of the proximal segment of the aorta above the sinotubular junction is linked to the constructive component of the LV myocardial work thus providing an alternative evidence for the LV ventricular–aorta coupling which was independent from aging.