Negative remodeling at the ostium of the left circumflex artery.

We report an ostial lesion with negative remodeling. Coronary angiography revealed a 60% stenosis at the ostium of the left circumflex artery (LCX). Intravascular ultrasound (IVUS)-guided directional atherectomy followed by stenting was planned. However, IVUS images revealed no significant stenosis and negative remodeling at the ostium of the LCX. The lesion did not undergo intervention.     

Small artery remodeling in hypertension

Hypertension is associated with altered structure of the resistance vessels, a process known as remodeling. This review summarizes current concepts concerning the structure of a subgroup of the resistance vessels, the small arteries, and the modes of remodeling, some of the determinants of remodeling, and some signaling pathways for remodeling. It is shown that the available evidence points to important roles for blood flow and growth factors, in addition to blood pressure, as causes of resistance artery remodeling. Finally, the relationship between vascular structure and blood pressure is discussed, in particular with regard to the effects of antihypertensive therapy. Here again, it appears that blood flow plays an important role in allowing the correction of the abnormal resistance vessel structure seen in hypertension.     

Obesity and carotid artery remodeling

Background/Objective:

The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions characterized by body size-dependent increase in stroke volume (SV) and blood pressure (BP).

Subjects/Methods:

Common carotid artery (CCA) luminal diameter (LD), IMT and CWS were measured in three different populations in order to study: (A) cross-sectional associations between SV, BP, anthropometric parameters and CCA LD (266 healthy subjects with wide range of body weight (24–159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects without CV complications and 88 non-obese subjects matched for gender and age).

Results:

CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was significantly higher (28±3 μm) as compared with those in the lower quartiles (8±3, 16±4 and 16±3 μm, P=0.001, P<0.05 and P=0.01, respectively). In addition, CCA CWS decreased during the observational period in the highest LD quartile (from 54.2±8.6 to 51.6±7.4 kPa, P<0.0001). As compared with gender- and age-matched lean individuals, obese subjects had highly increased CCA LD and BP (P<0.0001 for both), but only slightly higher CWS (P=0.05) due to a significant increase in IMT (P=0.005 after adjustment for confounders).

Conclusions:

Our findings suggest that in obese subjects, the CCA wall thickens to compensate the luminal enlargement caused by body size-induced increase in SV, and therefore, to normalize the wall stress. CCA diameter in obesity could represent an additional biomarker, depicting the impact of altered hemodynamics on arterial wall.     

Vascular remodeling after carotid artery stenting

Carotid stenting is an alternative to endarterectomy for the treatment of carotid stenosis. To determine the role of vascular remodeling after stent placement, we studied 19 high surgical risk patients undergoing carotid stenting for severe stenosis. Using high-resolution ultrasound, we evaluated the intima-media thickness (IMT), the intima-intima diameter, and the adventitia-adventitia diameter at prespecified sites of the carotid artery tree during 3 years of follow-up. The IMT of internal carotid artery, at the site of maximum stenosis, increased significantly from 0 mm after 24 hours, to 0.41 mm at 3 months, to 0.48 mm at 6 months, and to 0.51 mm at 3 years of follow-up. In the same site, diameters and residual stenosis (range 29-24%) did not change over time. Our study showed that stent is self-expanding against the atherosclerotic plaque within the 3-year follow-up period. Despite neointima formation, the intima-intima diameter does not change without worsening of the residual stenosis.     

Small artery remodeling in diabetes mellitus

AimsTo briefly review available data regarding changes in the structure of microvessels observed in patients with diabetes mellitus, and possible correction by effective treatment.Data synthesisThe development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small arteries' smooth muscle cells are restructured around a smaller lumen and there is no net growth of the vascular wall, while in some secondary forms of hypertension, hypertrophic remodeling may be detected. Moreover, in non-insulin-dependent diabetes mellitus hypertrophic remodeling of subcutaneous small arteries is present. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive and diabetic patients, over and above all other known cardiovascular risk factors. Therefore, regression of vascular alterations is an appealing goal of antihypertensive treatment. Different antihypertensive drugs seem to have different effects on vascular structure. In diabetic hypertensive patients, a significant regression of structural alterations to the small resistance arteries with drugs blocking the renin-angiotensin system (ACE inhibitors, angiotensin II receptor blockers) was demonstrated.ConclusionAlterations in the microcirculation represent a common pathological finding, and microangiopathy is one of the most important mechanisms involved in the development of organ damage as well as of clinical events in patients with diabetes mellitus. Renin-angiotensin system blockade seems to be effective in preventing and/or regressing alterations in the microvascular structure.     

动脉重塑与冠状动脉疾病

冠状动脉疾病的出现并不是动脉内膜中粥样斑块逐渐生长而导致血管腔狭窄的过程 ,直到狭窄程度达到一定的百分比之后血管腔才会减小 ,这是由于动脉重塑的存在而形成的。近年来 ,由于血管内超声成像的出现 ,使得在体内对动脉重塑进行研究成为可能。本文综述动脉重塑在冠状动脉疾病进展与消退中的作用、动脉重塑的病理生理机制和临床意义、以及动脉重塑在冠状动脉介入治疗术后再狭窄中的作用。     

Intravascular ultrasonic analysis of plaque characteristics associated with coronary artery remodeling.

We sought to determine the patient and plaque characteristics associated with the different forms of arterial remodeling as seen by intravascular ultrasound (IVUS) before coronary intervention. Remodeling in response to plaque accumulation may occur in the form of compensatory enlargement and/or focal vessel contraction. Previous studies report variation in the frequency and form of arterial remodeling. We performed preintervention IVUS imaging on 169 patients. Vessels were categorized as exhibiting compensatory enlargement or focal contraction if the arterial area at the lesion was larger or smaller, respectively, than both proximal and distal reference arterial areas; otherwise the artery was considered not to have undergone significant remodeling. Calcification was assessed and noncalcified plaque density was measured by videodensitometry. Sixty-one of 169 patients (66 narrowings) (46 men and 15 women, age 56+/-11 years) had adequate reference segments. Remodeling occurred in 43 of 66 patients (65%): compensatory enlargement in 27 of 66 (41%) and focal contraction in 16 of 66 (24%). Lesions with focal contraction had significantly smaller arterial area (13.3+/-3.3 vs. 18.1+/-7.0 mm2, p = 0.02) and plaque area (9.5+/-2.8 vs 13.7+/-5.5 mm2, p<0.01). Cross-sectional stenosis was similar (71+/-9% vs. 75+/-10%, p = NS), as was plaque density (p = 0.20), eccentricity, and calcium. Patient age, gender, and lesion location were not related to the form of remodeling. Similarly, history of diabetes, hypercholesterolemia, or hypertension was not predictive. Smoking was the only risk factor associated with focal contraction (p<0.01). Thus, whereas compensatory enlargement appears to be the most common form of coronary artery remodeling, focal contraction occurs more often in smokers.     

Small artery remodeling in hypertension and diabetes

The development of structural changes in the systemic vasculature is the end result of established hypertension. In essential hypertension, small artery smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, whereas in some secondary forms of hypertension and in non-insulindependent diabetes mellitus, a hypertrophic remodeling may be detected. Indices of small resistance artery structure, such as the tunica media to internal lumen ratio, may have a strong prognostic significance in hypertensive patients. Various antihypertensive drugs seem to have different effects on vascular structure. A complete normalization of small resistance artery structure was demonstrated in hypertensive patients, after prolonged and effective therapy with angiotensin-converting enzyme inhibitors, angiotensin II-receptor blockers, and calcium antagonists. Few data are available in diabetic hypertensive patients; however, blockade of the renin-angiotensin system seems to be effective in this regard.     

Small artery remodeling depends on tissue-type transglutaminase

Remodeling of small arteries is essential in the long-term regulation of blood pressure and blood flow to specific organs or tissues. A large part of the change in vessel diameter may occur through non-growth-related reorganization of vessel wall components. The hypothesis was tested that tissue-type transglutaminase (tTG), a cross-linking enzyme, contributes to the inward remodeling of small arteries. The in vivo inward remodeling of rat mesenteric arteries, induced by low blood flow, was attenuated by inhibition of tTG. Rat skeletal muscle arteries expressed tTG, as identified by Western blot and immunostaining. In vitro, activation of these arteries with endothelin-1 resulted in inward remodeling, which was blocked by tTG inhibitors. Small arteries obtained from rats and pigs both showed inward remodeling after exposure to exogenous transglutaminase, which was inhibited by addition of a nitric oxide donor. Enhanced expression of tTG, induced by retinoic acid, increased inward remodeling of porcine coronary arteries kept in organ culture for 3 days. The activity of tTG was dependent on pressure. Inhibition of tTG reversed remodeling, causing a substantial increase in vessel diameter. In a collagen gel contraction assay, tTG determined the compaction of collagen by smooth muscle cells. Collectively, these data show that small artery remodeling associated with chronic vasoconstriction depends on tissue-type transglutaminase. This mechanism may reveal a novel therapeutic target for pathologies associated with inward remodeling of the resistance arteries.     

Effects of lipid-lowering therapy on coronary artery remodeling

BACKGROUND: Although lipid-lowering therapy affects the luminal size of atherosclerotic coronary arteries the role of vascular remodeling has not been systematically studied. DESIGN/METHODS: Serial three-dimensional volumetric intravascular ultrasound (IVUS) was used to study remodeling, which was defined as changes in arterial size independent of or dependent on changes in plaque size. Using an automated contour detection algorithm, a 1 mm segment of a moderate atherosclerotic lesion at the site of the maximal plaque volume at baseline was analysed. After 12 months the relationship between the absolute change in vessel volume and plaque volume was calculated in 99 patients. There was a significant relationship between changes in plaque and vessel volume, independent of plaque progression or plaque regression (decrease in plaque size, r = 0.60, P < 0.0001 and increase in plaque size, r = 0.49, P < 0.0008, respectively; the slopes of the regression equation were 1.03 and 0.80). By means of an analysis of covariance we tested whether the regression slopes were equal between groups of patients as defined by the low-density lipoprotein-cholesterol (LDL-c) level achieved with lipid-lowering therapy. RESULTS: Only patients with plaque progression and a LDL-c level < 100 mg/dl had a significantly smaller slope than patients with a LDL-c level > 100 mg/dl (-0.14 compared with 1.14, P = 0.003 ), indicating diminished coronary remodeling. CONCLUSIONS: Serial volumetric IVUS confirms the existence of both positive and negative remodeling in relation to an increase and decrease in plaque volume. It has been shown that the outward remodeling process is diminished in patients with plaque progression and intensive lipid-lowering therapy.     

Coronary artery restenosis after atherectomy is primarily due to negative remodeling.

The primary cause of restenosis following directional coronary atherectomy (DCA) remains obscure. "Negative remodeling," a decrease in vessel area, is believed to be more causative than is increase in plaque area. The DCA technique used in these patients, designed to facilitate the removal of plaque, should allow a more precise evaluation of the relative roles of these two mechanisms. Twenty-five patients underwent DCA. In 17, complete angiographic and intravascular ultrasound (IVUS) images were obtained before and after DCA and at follow-up (6 to 9 months). Internal elastic lamina (IEL), lumen, and plaque areas were calculated at preatherectomy, postatherectomy, and follow-up. Postatherectomy, the mean IEL area increased by 32% and the mean plaque area decreased by 51%, resulting in a significant mean increase in lumen area, 500%. At follow-up when compared to postatherectomy, the change in IEL area was variable; however, the mean did not change significantly (p = 0.58). Plaque area change, when standardized for initial vessel size, was small (mean increase 2.8 +/- 3.5%). The mean lumen area did not decrease significantly at follow-up (p = 0.43). A highly significant correlation (r = 0.96) was noted between IEL area change and lumen area at follow-up. In contrast, the correlation between plaque area change and lumen area change over the same period was much less significant (r = 0.64). These data indicate that decrease in IEL area primarily is responsible for restenosis.     

Intravascular ultrasound analysis of arterial remodeling in the double-injury swine coronary artery model of restenosis.

BACKGROUND: Vascular remodeling is a major component of atherosclerotic and restenotic processes. The aim of this study was to evaluate remodeling at two different axial loci in a restenotic (double-injury) coronary artery model in the hypercholesterolemic minipig. METHODS: The cross-sectional area (CSA) of the lumen, artery and neointima following a single stenotic injury (SI) and second restenotic injury (RI) was measured by serial intravascular ultrasound (IVUS). IVUS CSAs were determined before, immediately after and 4 weeks after each injury. Analyses were performed at two selected axial loci, defined as: 1) locus of the minimal luminal area (MLA) 4 weeks after SI (measured immediately prior to the RI); and 2) locus of the MLA at 4 weeks after RI. Loci were selected to mimic diverse approaches used in studies of remodeling. RESULTS: Restenotic remodeling, defined by locus 1, was unchanged 4 weeks following the RI and neointima formation accounted for the chronic lumen loss. In contrast, constrictive remodeling was the prominent arterial response defined by locus 2. Regardless of the MLA analysis, artery wall enlargement occurred in more than half of the pigs at 4 weeks following the SI. Balloon/artery ratios were comparable during the two injuries and could not account for observed differences in remodeling. Remodeling results obtained by comparison of artery CSA to a reference CSA differed from serial IVUS analysis. CONCLUSIONS: In the presence of a pre-established stenosis, vascular remodeling depends on the axial locus of interest. In contrast, remodeling following injury of a na?ve artery is independent of defined axial locations used here and is predominantly one of outward remodeling.     

Volumetric remodeling of the proximal left coronary artery: early versus late after heart transplantation.

OBJECTIVES: The aim of this study was to characterize progression of cardiac allograft vasculopathy (CAV) with special respect to coronary artery geometry. BACKGROUND: As previously shown by intravascular ultrasound (IVUS), CAV is characterized by a multifocal intimal hyperplasia. Little is known, however, about vascular remodeling processes influencing vessel geometry and luminal narrowing. METHODS: In 30 heart transplant recipients serial IVUS studies were performed at baseline (BL) and after a mean follow-up period of 12.5+/-2.5 months. Changes in plaque, lumen and vessel volume were assessed in the proximal left anterior descending artery. Pattern of remodeling was analyzed in patients "early" (n = 15, BL study 1.4+/-0.7 months after heart transplantation [HTX]) compared with "late" after HTX (n = 15, BL 46.1+/-29.1 months). RESULTS: Plaque volume was found to increase by a mean of 23.8+/-25.9 mm3, not significantly different within and beyond the 1st year after HTX. Significant differences, however, were observed in changes in vessel volume with a mean decrease of -52.8+/-70.9 mm3 in the early group, whereas late follow-up group presented with an enlargement of 32.3+/-46.0 mm3. Based on these changes, lumen volume decreased by -73.2+/-69.8 mm3 early, in contrast to a slight increase of 5.2+/-32.6 mm3 in the late group. CONCLUSIONS: Progression of CAV is a complex process, modified by changes in the vascular geometry. Especially within the 1st year after HTX, luminal loss is influenced not only by an increase in plaque area but by a decrease in total vessel volume as well.     

Vascular remodeling of the carotid artery in patients with untreated essential hypertension increases with age.

We examined whether hypertrophy of the carotid artery in patients with untreated essential hypertension is associated with compensatory carotid artery enlargement as these patients age. Carotid ultrasonography was evaluated in 163 patients with untreated essential hypertension (74 males and 89 females) and in 76 normotensive subjects. Intima-media end-diastolic thickness (IMT) and outer vessel diameter (VD) were measured, and relative wall thickness (IMT/R, R=VD/2) and vascular mass (VM) were calculated. Determinants of vascular hypertrophy in patients with untreated essential hypertension were also investigated. VD, VM, and IMT were significantly correlated with age in both the normotensive and hypertensive groups. Additionally, IMT was significantly correlated with VD in both groups. There was no correlation between increasing age and IMT/R in either group. IMT, VD and VM were significantly higher in the hypertensive group >50 years than in age-matched normotensive controls. However, IMT/R was significantly higher in the 50-59 years hypertensive group than in normotensive controls of the same age group. In addition to age, VM was related to systolic blood pressure, pulse pressure, fasting blood sugar, IMT, VD, and IMT/R in the hypertensive group. Multivariate regression analysis in the hypertensive group indicated that IMT/R was the strongest predictor of carotid vascular mass. Age and pulse pressure were also independently related to vascular mass. These results indicate that, as patients with untreated hypertension age, carotid arteries undergo remodeling. This should add further impetus to the implementation of appropriate hypertension treatment for such patients.     

Long-term positive remodeling of the right coronary artery after reimplantation from the pulmonary artery to the ascending aorta

A 53-year-old woman, nonsmoking patient, with a history of surgically corrected anomalous origin of the right coronary artery from the pulmonary artery 17 years prior to admission, presented to our department complaining of mild, left-sided exertional chest pain for the past 3 months. She underwent a computed tomography examination of the heart and coronary angiography revealing postsurgical changes to the coronary vasculature and severe stenosis of the left circumflex artery, which was successfully treated by percutaneous stent implantation.