Yiqihuoxuejiedu Formula Inhibits Vascular Remodeling by Reducing Proliferation and Secretion of Adventitial Fibroblast after Balloon Injury

Vascular remodeling occurs in atherosclerosis, hypertension, and restenosis after percutaneous coronary intervention. Adventitial remodeling may be a potential therapeutic target. Yiqihuoxuejiedu formula uses therapeutic principles from Chinese medicine to supplement Qi, activate blood circulation, and resolve toxin and it has been shown to inhibit vascular stenosis. To investigate effects and mechanisms of the formula on inhibiting vascular remodeling, especially adventitial remodeling, rats with a balloon injury to their common carotid artery were used and were treated for 7 or 28 days after injury. The adventitial area andα-SMA expression increased at 7 days after injury, which indicated activation and proliferation of adventitial fibroblasts. Yiqihuoxuejiedu formula reduced the adventitial areas at 7 days, attenuated the neointima and vessel wall area, stenosis percent, andα-SMA expression in the neointima, and reduced collagen content and type I/III collagen ratio in the adventitia at 28 days. Yiqihuoxuejiedu formula had more positive effects than Captopril in reducing intimal proliferation and diminishing stenosis, although Captopril lowered neointimalα-SMA expression and reduced the collagen content at 28 days. Yiqihuoxuejiedu formula has inhibitory effects on positive and negative remodeling by reducing adventitial and neointimal proliferation, reducing content, and elevating adventitial compliance.

Abstract 348: Serial MRI Differentiates the Natural History of Stable and Vulnerable Plaques in a Rabbit Aorta

Non-invasive monitoring of human atherosclerotic plaque progression would be extremely valuable for determining the characteristics of vulnerable plaques before they rupture and for evaluating therapeutic interventions. We have shown that MRI is a reliable method for differentiating stable and vulnerable aortic atherosclerotic plaques in a rabbit model of atherothrombosis. In this study, we imaged rabbits at 4 time points (baseline, 1, 2 and 3 months) to monitor the progression of plaques and investigate when stable and vulnerable plaques can be differentiated. MR images and histology of two plaques in the same rabbit aorta are compared below. The top row of black blood (BB) T1 images (with fat suppression) show no significant changes in the lumen or the vessel wall area, and no thrombus in the stable plaque after triggering to induce plaque rupture. The histology showed an intact fibrous cap, overlying diffuse lipids. In comparison, there is a marked increase in vessel wall area in the vulnerable plaque (from 4.1 to 15 mm2 over 3 months). The second row (T1BB FS with Gd) shows some uptake of Gd into the stable plaque and surrounding tissue, but the vulnerable plaque showed rapidly increased Gd uptake between months 2 and 3. The vulnerable plaque also showed a large luminal thrombus in the MR images of the live rabbit and in the corresponding histology slice. In addition, the vulnerable plaque showed excessive outward remodeling at 2 months (data not shown). Our study shows a progression of vulnerable features, clearly evident at 2 months, in the plaque that disrupted. We are currently investigating whether therapies initiated at 2 months will reduce the progression of plaque vulnerability.

Bordered pit and ray morphology involvement in elm resistance to Ophiostoma novo-ulmi

The main objective of this study was to identify differential anatomical features between Ulmus pumila L. and Ulmus minor Mill. clones resistant to Dutch elm disease and U. minor clones susceptible to Dutch elm disease, with a focus on the intervascular pits and medullary rays. Resistant elms showed lower mean values than susceptible elms for pit membrane diameter, pit aperture area, pit membrane abundance per vessel-wall area, ray width, and ray tangential area. A principal component analysis of the parameters measured revealed slight differentiation between species but clearly grouped U. minor clones according to their susceptibility group. In comparison with susceptible elms, the pit structure observed in resistant elms may limit passive fungal spread within the sapflow, lower the probability of fungal cells passively reaching pit membranes, and reduce the vulnerability of the xylem to cavitation. Similarly, the ray structure observed in the resistant elms is likely to reduce the amount of easily accessible nutrients available for fungal growth as well as the rate of radial colonization in comparison with susceptible elms. Examination of the principal component loadings suggested that susceptible U. minor clones were mainly characterized by enhanced values of pit membrane abundance per vessel-wall area relative to resistant U. minor trees.

Vascular injury response in mice is dependent on genetic background

Mouse models are employed to unravel the pathophysiology of vascular restenosis. Although much effort has been spent on how to apply an adequate arterial injury, the influence of the genetic background of mice has not yet received sufficient consideration. The study presented herein was designed to demonstrate the influence of the mouse strain on vascular injury response. Mice of a defined background (50% 129 strain and 50% DBA strain) were backcrossed into either the 129 strain or the DBA strain. Male offspring were subjected to a femoral artery injury model by applying an electric current. Morphometric analysis revealed that backcrossing into the 129 strain resulted in a significant ( P < 0.001) 17-fold increase in neointima formation ( n = 17 mice) compared with backcrossing into the DBA strain ( n = 19). The values of neointima area were 9.18 × 103 ± 2.13 × 103 and 0.54 × 103 ± 0.39 × 103 μm2, respectively. In conjunction, the vessel wall area was enhanced by 1.8-fold ( P < 0.001). In contrast, no significant differences were found for the areas of the lumen and the tunica media. Similarly, a significant increase in neointima formation was also found for mice of pure 129 strain compared with pure DBA strain. The results underline the importance of the genetic background for studies on vascular injury response. Furthermore, because the mouse genome of the various strains is well defined, serial testing of the genetic background of mice will provide candidate genes and/or genetic modifiers controlling vascular injury response.

Cerebral vascular autoregulation of blood flow and tissue PO2 in diabetic rats

The effect of chronic, severe diabetes mellitus on the morphology, blood flow regulation, and tissue PO2 of the cerebral cortex was evaluated in adult rats. The arterioles of the diabetic animals were enlarged in terms of both lumen diameter and vessel wall area. Although resting blood flow in the diabetic rats was greater than in the normal rats, the autoregulation of cerebral blood flow was very good within an arterial pressure range of 40-150 mmHg, just as in normal rats. The resting tissue PO2 in diabetic rats was 14.9 +/- 0.5 (SEM) compared with 12.7 +/- 0.6 mmHg in normal animals and in both groups remained at or near the resting PO2 at arterial pressures from 40 to 150 mmHg. There was no apparent loss of arterioles on the cortex surface or change in length of individual arterioles in diabetic animals but there was a 20-30% decrease in the number of venules and no change in the length of individual venules. These data indicate that although the arteriolar morphology and number of venules change in the brain during diabetes, physiological function in terms of tissue PO2 and blood flow regulation is maintained within normal limits.