Coronary Artery Remodeling Research Articles

LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study

Aims To investigate the relationship between coronary artery remodelling and glycaemic and lipid profiles in diabetic patients. Methods and results Intravascular ultrasound analyses of 131 angiographically non-significant coronary stenoses in 80 diabetic patients were performed. The remodelling index (RI) was calculated as the ratio between total vessel area at target site and total vessel area at proximal reference, and was assessed in two ways: as a continuous variable, and as a binary categorical variable: RI<1 namely, negative remodelling (group I), or RI≥1 (group II). Percentage cross-sectional narrowing was 57±13%. On average, RI was 0.93±0.13. Coronary shrinkage was found in 94 (71.7%) lesions. Significant inverse correlations were demonstrated between RI and total cholesterol ( r =–0.26, P =0.003), apolipoprotein-B ( r =–0.23, P =0.01) and LDL-cholesterol ( r =–0.3, P =0.001) levels. Multivariable lineal regression analysis identified LDL-cholesterol as the only independent predictor of RI ( P =0.001). Conclusion Negative remodelling is a frequent finding in diabetics and it is associated with LDL-cholesterol levels. This may contribute to the diffuse coronary artery disease observed in diabetic patients.

LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study: reply

LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study: reply

LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study

To investigate the relationship between coronary artery remodelling and glycaemic and lipid profiles in diabetic patients. Intravascular ultrasound analyses of 131 angiographically non-significant coronary stenoses in 80 diabetic patients were performed. The remodelling index (RI) was calculated as the ratio between total vessel area at target site and total vessel area at proximal reference, and was assessed in two ways: as a continuous variable, and as a binary categorical variable: RI<1 namely, negative remodelling (group I), or RI> or =1 (group II). Percentage cross-sectional narrowing was 57+/-13%. On average, RI was 0.93+/-0.13. Coronary shrinkage was found in 94 (71.7%) lesions. Significant inverse correlations were demonstrated between RI and total cholesterol (r=-0.26, P=0.003), apolipoprotein-B (r=-0.23, P=0.01) and LDL-cholesterol (r=-0.3, P=0.001) levels. Multivariable lineal regression analysis identified LDL-cholesterol as the only independent predictor of RI (P=0.001). Negative remodelling is a frequent finding in diabetics and it is associated with LDL-cholesterol levels. This may contribute to the diffuse coronary artery disease observed in diabetic patients.

Computed Tomography Assessment of the Regression of an Atherosclerotic Coronary Artery Plaque

Multislice spiral computed tomography (MSCT) permits the noninvasive visualization of coronary artery stenoses and occlusions, as well as atherosclerotic plaques, in patients with coronary artery disease. This report describes a patient with stable angina pectoris in whom the regression of the plaque and coronary artery remodeling was documented by serial MSCT.

Epicardial Coronary Artery Remodeling in Systemic Hypertension

Epicardial Coronary Artery Remodeling in Systemic Hypertension

Differential Effect of Experimental Hypertension and Hypercholesterolemia on Adventitial Remodeling

Intima-media remodeling, as frequently assessed by changes in the external elastic lamina-to-lumen area (EELLA), is well-described in coronary artery disease in contrast to adventitial remodeling, especially in the early disease stage. Female domestic pigs were randomized to one of the following 12-week treatment groups: normal diet (N; n=6), high-cholesterol diet (HC; n=6), or renovascular hypertension (HT; n=4). Low-density lipoprotein (LDL) cholesterol serum concentration was higher in HC than in N and HT (395.5+/-106 versus 38.6+/-14 and 37.2+/-6.8 mg/dL; P<0.05 for both). Mean arterial pressure was higher in HT than in N and HC (141.3+/-21 versus 107.4+/-8.9 and 109.4+/-7.8 mm Hg; P<0.05 for both). EELLA ratio, as assessed by morphometry, was similar in N, HC, and HTN (1.03+/-0.32 versus 0.95+/-0.29 and 1.01+/-0.09; P<0.05 for both). Coronary vasa vasorum density, as assessed by 3-dimensional micro-computed tomography, was higher in HC than in N and HT (3.4+/-1.0 versus 1.9+/-0.3 and 2.0+/-1.2; P<0.05 for both). In contrast, immunostaining showed a higher collagen III content and the presence of adventitial myofibroblasts in HT compared with N and HC. The current study suggests that adventitial remodeling precedes intima and media remodeling of coronary arteries early after exposure to hypercholesterolemia and hypertension, with distinct qualitative differences between them. Intima-media remodeling is well-described in coronary artery disease in contrast to adventitial remodeling. Results of the current study on coronary arteries of pigs, randomized to 12 weeks of normal diet (N), hypercholesterolemic diet (HC), or renovascular hypertensive (HT), indicate that adventitial remodeling precedes intima-media remodeling early after risk factor exposure with distinct qualitative differences.

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.

Spectrum of remodeling behavior observed with serial Long-Term (≥12 months) Follow-Up intravascular ultrasound studies in left main coronary arteries

Most intravascular ultrasound (IVUS) studies of arterial remodeling in native coronary arteries reported a remodeling index obtained at a single time point. We analyzed serial IVUS examinations, including the vessel cross-sectional area changes (remodeling behavior), of 60 hemodynamically nonstenotic left main lesions (baseline vs 18.4 ± 9.4 months follow-up). Lumen reduction resulted from vessel reduction (sometimes despite plaque + media decrease), plaque + media increase (with or without vessel increase), or both. The percent annual changes in lumen area correlated strongly with changes in vessel (r = 0.84), but not with changes in plaque + media area. Plaques were classified as group A lesions, reflecting positive remodeling behavior (vessel changes >0), or group B lesions, reflecting negative (or intermediate) remodeling behavior (vessel changes ≤0). Both groups did not differ significantly in demographics, laboratory data, and medications. Group A lesions (n = 40) more often showed plaque + media increase than group B lesions (32 of 40 [80%] vs 9 of 20 [45%]; p = 0.02). Group A lesions had, on average, mild annual lumen increase despite mild plaque + media increase, i.e, overcompensation of remodeling for plaque + media increase (vessel increase greater than plaque + media area increase, 19 of 40 [47%]). Conversely, group B lesions (n = 20) showed a significant lumen area reduction (−2.8 ± 2.6 mm 2/year) as a result of a decrease in vessel area only. Thus, serial long-term reduction of lumen size may result from vessel shrinkage (sometimes despite plaque decrease), plaque increase (with or without vessel increase), or both; overall, only the remodeling behavior has a significant relation to lumen changes. More than 30% of lesions show a negative remodeling behavior, which shows no relation to patient characteristics or initial plaque burden.

1026-59 Elevated high-sensitivity C-reactive protein was associated with coronary artery remodeling in patients with unstable angina

1026-59 Elevated high-sensitivity C-reactive protein was associated with coronary artery remodeling in patients with unstable angina

1038-151 Noninvasive assessment of coronary artery remodeling by multislice computed tomography

1038-151 Noninvasive assessment of coronary artery remodeling by multislice computed tomography

Interferon-gamma plays a nonredundant role in mediating T cell-dependent outward vascular remodeling of allogeneic human coronary arteries.

Vascular remodeling (change in vessel diameter) rather than intimal hyperplasia is the most important predictor of luminal loss in immune-mediated arterial injury, yet little is known about its mechanisms. Here, we show that outward vascular remodeling and intimal thickening, two manifestations of arteriosclerosis with opposing effects on luminal size, result from immune effector mechanisms that are T-cell dependent and interferon (IFN)-gamma mediated. In our in vivo model of human coronary artery injury by allogeneic peripheral blood mononuclear cells, both processes occur concurrently and are characterized by T-cell infiltrates with a predominantly IFN-gamma-producing cytokine profile. Neutralization of IFN-gamma inhibits the arterial and intimal expansion, whereas administration of IFN-gamma enhances these effects. The nonredundant role of IFN-gamma in T-cell-dependent remodeling of human coronary arteries demonstrated here presents a new therapeutic target for preservation of vessel lumen in arteriosclerosis.

Evaluation of Coronary Artery Remodeling in Patients With Acute Coronary Syndrome and Stable Angina by Multislice Computed Tomography

Multislice computed tomography (MSCT) was used to evaluate coronary artery remodeling in patients with acute coronary syndrome (ACS) and stable angina (SA). MSCT was performed in 31 patients with ACS and 26 patients with SA and intravascular ultrasound (IVUS) was performed in 28 of these 57 patients. In both the MSCT and IVUS analyses, coronary artery remodeling was assessed by the remodeling index (RI): RI >1.10 was defined as positive coronary artery remodeling (PCAR) and RI <0.95 was defined as negative coronary artery remodeling (NCAR). The RI assessed by MSCT closely correlated with that of IVUS (r=0.86, n=28). The vessel area at the region of maximum luminal narrowing was also comparable between the MSCT and IVUS measurements (r=0.92). PCAR was present in 19 patients (61.3%) with ACS, but in none of the patients with SA (p<0.0001). However, NCAR was present in only 1 patient with ACS (3.2%), but was present in 18 patients (62.9%) with SA. The RI was significantly larger in patients with ACS (1.19+/-0.18) than in those with SA (0.89+/-0.10, p<0.0001). MSCT accurately assesses coronary artery remodeling.

The Effects of Coronary Artery Remodeling on the Developments of Collateral Blood Flow in Patients with Acute Myocardial Infarction Treated with Primary Angioplasty

Background: The relation between pressure-derived fractional collateral flow (PDCF) and coronary arterial remodeling remains uncertain in acute myocardial infarction. Methods: We evaluated the effect of arterial remodeling on the development of PDCF in 72 patients with first acute myocardial infarction (pain onset 1.0 and nonpositive remodeling as a RI ≤1.0. Using a 0.014-in. fiber optic pressure moni- toring guide wire, the PDCF index was measured by simultaneous measurement of mean aorta pressure (Pao), distal coronary pressure during the balloon occlusion (Pocc), and central venous pressure (CVP): PDCF index= 100×(Pocc-CVP)/(Pao-CVP). Sufficient collateral was defined as PDCF index >24% and insufficient collateral as PDCF index ≤24%. Results: The RI was 1.04±0.15 in the lesions with sufficient collateral and 1.03±0.16 in the lesions with insufficient collateral (p=0.812). There was no significant difference in the frequency of positive remodeling between the 2 groups (55% vs. 54%, respectively, p=0.966). The PDCF index was 20±11% and 20± 9% in positive and nonpositive remodeling, respectively (p=0.891). There was no significant correlation between RI and PDCF index (r=0.027, p=0.823). Conclusions: The pattern of coronary arterial remodeling might not influence the development of collateral blood flow in patients with acute myocardial infarction treated with primary

Can angiotensin II type 2 receptors have deleterious effects in cardiovascular disease? Implications for therapeutic blockade of the renin-angiotensin system.

The renin–angiotensin system (RAS) plays a major role in regulating the cardiovascular system, and disorders of the RAS contribute largely to the pathophysiology of hypertension, renal diseases, and chronic heart failure. Two subtypes of angiotensin II (Ang II) receptors have been defined on the basis of their differential pharmacological and biochemical properties: Ang II type 1 receptors (AT1), which are involved in most of the well-known physiological effects of Ang II, and Ang II type 2 receptors (AT2), which have a less well-defined role but appear capable of counterbalancing some of the effects of AT1 stimulation. The 2 receptors, both of which belong to the superfamily of G-protein–coupled receptors, are believed to have different signaling pathways and different functions.1 AT1 transactivates growth pathways and mediates major Ang II effects such as vasoconstriction, increased cardiac contractility, renal tubular sodium reabsorption, cell proliferation, vascular and cardiac hypertrophy, inflammatory responses, and oxidative stress. AT2 is believed to induce essentially opposite effects, including vasodilation and antigrowth and antihypertrophic effects,1–3 and to play a significant role in blood pressure (BP) regulation.4 The 2 major pharmacological inhibitors of the RAS, which are now important elements in the treatment of hypertension and cardiovascular disease, are ACE inhibitors and angiotensin receptor blockers (ARBs). These 2 classes of drugs have different effects on the RAS: suppression of Ang II production by ACE inhibitors reduces activation of both Ang II receptor subtypes, whereas ARBs preferentially block AT1 and leave AT2 unopposed. Long-term administration of ARBs results in a several-fold increase in plasma Ang and thus a possible overstimulation of AT2. It is generally accepted that the effects of stimulation of AT2 on the cardiovascular system are beneficial and that no harm would result from increased activation of …

Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling.

Multiple lines of evidence establish that angiotensin II (Ang II) induces not only hypertension but also directly contributes to cardiac diseases. Apoptosis signal-regulating kinase 1 (ASK1), one of mitogen-activated protein kinase kinase kinases, plays a key role in stress-induced cellular responses. However, nothing is known about the role of ASK1 in cardiac hypertrophy and remodeling in vivo. In this study, by using mice deficient in ASK1 (ASK1-/- mice), we investigated the role of ASK1 in cardiac hypertrophy and remodeling induced by Ang II. Left ventricular (LV) ASK1 was activated by Ang II infusion in wild-type mice, which was mediated by angiotensin II type 1 receptor and superoxide. Although Ang II-induced hypertensive effect was comparable to wild-type and ASK1-/- mice, LV ASK1 activation by Ang II was not detectable in ASK1-/- mice, and p38 and c-Jun N-terminal kinase (JNK) activation was lesser in ASK-/- mice than in wild-type mice. Elevation of blood pressure by continuous Ang II infusion was comparable between ASK1-/- and wild-type mice. However, Ang II-induced cardiac hypertrophy and remodeling, including cardiomyocyte hypertrophy, cardiac hypertrophy-related mRNA upregulation, cardiomyocyte apoptosis, interstitial fibrosis, coronary arterial remodeling, and collagen gene upregulation, was significantly attenuated in ASK1-/- mice compared with wild-type mice. These results provided the first in vivo evidence that ASK1 is the critical signaling molecule for Ang II-induced cardiac hypertrophy and remodeling. Thus, ASK1 is proposed to be a potential therapeutic target for cardiac diseases.

Late incomplete apposition with excessive remodeling of the stented coronary artery following intravascular brachytherapy

Intravascular brachytherapy may cause “exaggerated” vessel remodeling with late incomplete apposition in segments that have little disease, which are exposed to higher radiation doses. The long-term clinical impact of this finding is unclear.

Coronary arterial remodeling in differing clinical presentations of unstable angina pectoris--an intravascular ultrasound study.

Coronary arterial remodeling influences the clinical presentation of ischemic heart disease; however, there is little information on the relationship between coronary arterial remodeling and the type of angina pectoris that patients manifest. The study was undertaken to determine the difference of coronary arterial remodeling in patients with different types of angina pectoris. We analyzed 100 patients with ischemic heart disease using intravascular ultrasound (IVUS). Intracoronary IVUS images of proximal reference (PR), distal reference (DR), and target lesion were recorded, and intraluminal area (LA) and external elastic membrane (EEM) were measured. We defined a remodeling index as 100 x (lesion EEM - [PR-EEM + DR-EEM]/2) / ([PR-EEM + DR-EEM]/2). Cases were classified into three groups according to the clinical history (Group 1a: de novo unstable angina pectoris, Group 1b: accelerating unstable angina pectoris, and Group 2; stable angina pectoris). The remodeling index in Group 1a was significantly larger than that in Groups 1b and 2 (18.6 +/- 28.5 vs. 5.3 +/- 27.1 and 18.6 +/- 28.5 vs. -2.7 +/- 17.6, p = 0.0347 and p = 0.0005, respectively), but there was no statistical difference in remodeling index between Groups 1b and 2. Our results indicate that positive coronary arterial remodeling is more prevalent in patients with new onset of angina pectoris. The specific type of coronary arterial remodeling may affect the clinical presentation of patients with coronary artery disease.

Correlation of coronary arterial remodeling determined by intravascular ultrasound with angiographic diameter reduction of 20% to 60%

Negative remodeling is commonly observed in stenotic coronary lesions. It is unknown whether negative remodeling is an early or late event. This study was designed to elucidate when negative remodeling occurs in the development of coronary stenosis. Remodeling was assessed by preintervention intravascular ultrasound in 104 native coronary lesions with intermediate stenosis (20% to 60% of diameter stenosis measured by quantitative coronary angiography). Positive remodeling was defined as lesion external elastic membrane (EEM) cross-sectional area (CSA) greater than the proximal reference, intermediate remodeling as lesion EEM CSA between those of the proximal and distal references, and negative remodeling as lesion EEM CSA less than the distal reference. Positive, intermediate, and negative remodeling were observed in 18%, 32%, and 50%, respectively, of lesions with intermediate stenosis. Lesions with negative and intermediate remodeling had more hard plaque compared with those with positive remodeling (79% vs 70% vs 42%, p = 0.02). Calcium was more frequent in lesions with negative and intermediate remodeling than in those with positive remodeling (52% vs 55% vs 16%, p = 0.01). Lesions with negative remodeling had smaller EEM CSA (11.5 ± 5.2 vs. 13.7 ± 3.4 vs 14.5 ± 5.6 mm 2, p = 0.03) and less plaque (7.9 ± 4.6 vs 10.8 ± 3.4 vs 10.8 ± 4.9 mm 2, p = 0.004) compared with positive and intermediate remodeling lesions, although lumen CSA (3.7 ± 1.7 vs 2.8 ± 0.8 vs 3.6 ± 1.3 mm 2, p = 0.1) and area stenosis (57 ± 15% vs 59 ± 14% vs 56 ± 10%, p = 0.7) were similar. Negative remodeling is frequently observed in lesions with intermediate stenosis. This suggests that negative remodeling occurs early in lesion formation.

Coronary arterial remodeling: from bench to bedside.

Coronary arterial remodeling describes changes of vessel size at the site of atherosclerotic lesions. Positive remodeling (expansion) of early lesions maintains lumen size despite plaque accumulation. In contrast, negative remodeling (shrinkage) contributes to luminal stenosis independent of plaque accumulation. Because of these adaptive changes, plaque progression/regression is not closely reflected in luminal size. Histologic studies have demonstrated that the pathophysiologic role of arterial remodeling is more complex than a mere compensatory process. Surprisingly, there is a consistent association between positive arterial remodeling, local inflammatory response, and plaque vulnerability. In vivo tomographic imaging techniques, in particular intravascular ultrasound, and potentially computed tomography and magnetic resonance imaging, allow the observation of remodeling in clinical settings. The integration of basic knowledge about arterial remodeling with clinical observations from in vivo imaging could lead to a better understanding of plaque progression, regression, and vulnerability and may eventually have implications for disease prevention.

Remodeling of human coronary arteries over time in vivo

Remodeling of human coronary arteries over time in vivo