The Role of Angiogenesis in Coronary Artery Disease: A Double-Edged Sword: Intraplaque Angiogenesis in Physiopathology and Therapeutic Angiogenesis for Treatment

2018 ◽  
Vol 24 (4) ◽  
pp. 451-464 ◽  
Author(s):  
Wen Wu ◽  
Xiaobo Li ◽  
Guangfeng Zuo ◽  
Jiangqin Pu ◽  
Xinlei Wu ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Plaque Rupture ◽  
Therapeutic Angiogenesis ◽  
Intraplaque Hemorrhage ◽  
Protein Therapy ◽  
Angiogenic Growth Factors ◽  
Coronary Syndrome ◽  
Artery Disease

Angiogenesis is described as a sprouting and growth process of new blood vessels from pre-existing vasculature. The relationship between angiogenesis and coronary artery disease (CAD) is double-sided. On one hand, angiogenesis within plaques is responsible for facilitating the growth and vulnerability of plaques by causing intraplaque hemorrhage and inflammatory cell influx, and overabundance of erythrocytes and inflammatory cells within a plaque probably causes plaque rupture, further leading to acute coronary syndrome. Therefore, inhibiting intraplaque angiogenesis has been considered as a potential therapeutic target for CAD. On the other hand, aiming at improving reperfusion to the ischemic myocardium in patients with CAD, angiogenesis promoting has been utilized as a therapeutic approach to expand myocardial microvascular network. Current strategies include direct administration of angiogenic growth factors (protein therapy), promoting angiogenic genes expression in vivo (gene therapy), and delivering stem cells (cell therapy) or exosomes (cell free therapy). This article will start by clarifying the basic concept of angiogenesis, interpret the mechanism of excessive intraplaque angiogenesis in atherosclerosis, and discuss its role in the growth and vulnerability of plaques. Then we will focus on the four distinct strategies of therapeutic angiogenesis. Despite promising animal studies and smallscale clinical trials of therapeutic angiogenesis in patients with ischemic heart disease, investigations have far not shown definite evidence of clinical efficacy. Hence, while acknowledging future work that remains to be done to validate the clinical results, we reviewed the critical challenges in this arena and highlighted the exciting progress that has occurred recently.

P2245Sex differences in the in-vivo markers of platelet activation among patients with ischemic heart disease: insights from the EVA study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Raparelli ◽  
G F Romiti ◽  
N Sperduti ◽  
G F Santangelo ◽  
M Vano ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Sex Differences ◽  
Coronary Artery ◽  
Coronary Stenosis ◽  
Clinical Presentation ◽  
Coronary Syndrome ◽  
Chronic Angina ◽  
Artery Disease

Abstract Background/Introduction Ischemic heart diseases (IHD) are not synonymous with obstructive flow-limiting coronary artery disease (CAD), especially in women. Platelet dysfunction is suggested as a potential mechanism favouring ischemia in non-obstructive CAD. However, it is unknown whether sex differences in platelet function of patients with non-obstructive CAD exist. Purpose We assessed for sex differences in in-vivo markers of platelet activation among patients with the acute coronary syndrome and chronic stable angina, with or without obstructive CAD Methods From the “Endocrine Vascular disease Approach” (EVA) study, we selected IHD patients undergoing urgent or elective coronary angiography with complete baseline clinical characteristics and angiographic data. Non-obstructive CAD was defined as the presence of coronary stenosis <50%. Thromboxane B2 (TxB2) and soluble P-selectin (sP-s) were measured at baseline. A sex-stratified analysis of platelet biomarkers was performed. Results Among two-hundred-seventy-seven patients (mean age 67±11, 37% women), non-obstructive CAD was documented in 25% of patients. Acute coronary syndrome (ACS) was the reason for angiography in 61% of cases. Women had more frequently ACS, as compared with men (54.8% vs 41.3%, p=0.001), with predominantly non-obstructive CAD. Median serum TxB2 (121.5 [92.7–174.0] vs 103.5 [83.0–140.2] pg/ml, p=0.005) and plasma sP-s (27.0 [18.7–35.0] vs 22.0 [16.0–30.0] ng/ml, p=0.006) levels were higher in patients with ACS as compared with the ones with stable chronic angina. The median concentration of TxB2 was significantly increased in women as compared with men, regardless of the clinical presentation and the coronary stenosis degree (all comparison, p<0.001). However, women with non-obstructive CAD were the group with the highest serum levels of TxB2 (140.0 [111.0–152.0] pg/ml). Sex differences in the plasma sP-s level were also observed among patients with stable chronic angina (women, 26 [20.0–34.0] vs men, 21 [16.6–27.7] ng/ml, p=0.002) and with non-obstructive CAD (women, 26 [20.5–34.5] vs men, 18.5 [16.6–26.0] ng/ml, p=0.003). Conclusion(s) Women with IHD and non-obstructive CAD had increased level of TxB2 and sP-s as compared with men, independently by the clinical presentation. Further investigations are warranted to verify the role of platelet hyperactivation in the pathogenesis of myocardial ischemia with non-obstructive coronary artery disease among women. Acknowledgement/Funding Scientific Independence of Young Researchers Program (RBSI14HNVT) - Ministry of Education, University and Research (MIUR)

scholarly journals AGE–RAGE Stress and Coronary Artery Disease

2021 ◽  
Author(s):  
Kailash Prasad
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Plaque Rupture ◽  
Serum Levels ◽  
Cell Receptor ◽  
Treatment Modalities ◽  
Coronary Artery Atherosclerosis ◽  
Artery Disease ◽  
Endogenous Secretory Rage

AbstractCoronary artery atherosclerosis and atherosclerotic plaque rupture cause coronary artery disease (CAD). Advanced glycation end products (AGE) and its cell receptor RAGE, and soluble receptor (sRAGE) and endogenous secretory RAGE (esRAGE) may be involved in the development of atherosclerosis. AGE and its interaction with RAGE are atherogenic, while sRAGE and esRAGE have antiatherogenic effects. AGE–RAGE stress is a ratio of AGE/sRAGE. A high AGE–RAGE stress results in development and progression of CAD and vice-versa. AGE levels in serum and skin, AGE/sRAGE in patients with CAD, and expression of RAGE in animal model of atherosclerosis were higher, while serum levels of esRAGE were lower in patients with CAD compared with controls. Serum levels of sRAGE in CAD patients were contradictory, increased or decreased. This contradictory data may be due to type of patients used, because the sRAGE levels are elevated in diabetics and end-stage renal disease. AGE/sRAGE ratio is elevated in patients with reduced or elevated levels of serum sRAGE. It is to stress that AGE, RAGE, sRAGE, or esRAGE individually cannot serve as universal biomarker. AGE and sRAGE should be measured simultaneously to assess the AGE–RAGE stress. The treatment of CAD should be targeted at reduction in AGE levels, prevention of AGE formation, degradation of AGE in vivo, suppression of RAGE expression, blockade of RAGE, elevation of sRAGE, and use of antioxidants. In conclusion, AGE–RAGE stress would initiate the development and progression of atherosclerosis. Treatment modalities would prevent, regress, and slow the progression of CAD.

Myocardial Infarction with Nonobstructive Coronary Artery Disease—Definition, Etiopathogenesis, Diagnosis, and Management

2021 ◽  
Author(s):  
Patrick Baghdasaryan ◽  
Balaji Natarajan ◽  
Madlena Nalbandian ◽  
Padmini Varadarajan ◽  
Ramdas G. Pai
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Plaque Rupture ◽  
Coronary Microvascular Dysfunction ◽  
Rare Presentation ◽  
Diagnosis And Management ◽  
Coronary Syndrome ◽  
Disease Definition ◽  
Artery Disease

AbstractMyocardial infarction with nonobstructive coronary arteries (MINOCA) is a complex clinical syndrome that is characterized by evidence of acute myocardial infarction in the absence of significant epicardial coronary artery disease on angiography. The term “MINOCA” encompasses a group of heterogeneous diseases with varying underlying mechanisms and each with its own pathophysiology. Overlooked plaque rupture or erosion and coronary vasospasm are the most common causes of MINOCA and can be diagnosed by routine intracoronary imaging and vasoreactivity testing, respectively. Coronary microvascular dysfunction is a less recognized, albeit an important cause of morbidity in patients presenting with MINOCA. Although MINOCA is a rare presentation of acute coronary syndrome, it is not a benign disorder and can have adverse consequences if untreated. In this article, we aim to review the pathogenesis, clinical characteristics, and finally propose a systematic approach in the diagnosis and management of patients with MINOCA.

Abstract 14829: Semi-quantitative Assessment of OCT-macrophage Predicts Future Development of Thin-cap Fibroatheroma in Non-culprit Lipid Plaques: A Serial Optical Coherence Tomography Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yoshiyasu Minami ◽  
Daniel S. Ong ◽  
Shiro Uemura ◽  
Zhao Wang ◽  
Aaron D. Aguirre ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Future Development ◽  
Area Under The Curve ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Artery Disease ◽  
The Impact

Introduction: Previous pathological studies have demonstrated that macrophages play an important role for the deterioration of fibrous cap and the onset of acute coronary syndrome. However, the significance of macrophage on the development of thin-cap fibroatheroma (TCFA) had not been fully evaluated in vivo. Aim: To explore the impact of OCT detected macrophage on the development of TCFA in patients with coronary artery disease using serial OCT images. Methods: A total of 152 non-culprit plaques from 90 patients who had serial OCT imaging at baseline and follow-up (median 6.38 [6.07-12.5] months) were included. TCFA was defined as the plaque with the fibrous cap thickness <65μm.OCT detected macrophage was semi-quantitatively assessed in every 1mm along the entire target plaque using a previously introduced grading system; Grade 0: no macrophage, Grade 1: localized macrophage accumulation, Grade 2: clustered accumulation<1 quadrant, Grade 3: clustered accumulation≥1 quadrant but <3 quadrants, Grade 4: clustered accumulation≥3 quadrants. The summation of 0 to 4 grades was evaluated. Results: Among 45 TCFA at baseline, 19 remain as TCFA [persistent TCFA] and 26 changed to non-TCFA [resolved TCFA] at follow-up (Figure). The macrophage grade in persistent TCFA was significantly greater than that in resolved TCFA (13.0 [8.00-17.0] vs. 4.00 [2.00-8.25] (P<0.001)) at baseline. On the other hand, 11 among 107 non-TCFA at baseline changed to TCFA [acquired TCFA] at follow-up. The macrophage grade in acquired TCFA was significantly greater than that in non-TCFA (14.0 [11.0-19.0] vs. 2.0 [0.00-6.75] (P<0.001)) at baseline. The macrophage grade>7.5 at baseline had good performance in discriminating TCFA from non-TCFA at follow-up (area under the curve [AUC] = 0.884, P<0.001) (Figure). Conclusions: The semi-quantitative evaluation of OCT detected macrophage at baseline had the potential to predict the future development of TCFA in patients with coronary artery disease.

Coronary artery disease in the elderly patient

2004 ◽  
Vol 14 (2) ◽  
pp. 105-118
Author(s):  
S. Joanna Cowell ◽  
David E. Newby ◽  
Nicholas A. Boon
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Angina ◽  
Plaque Rupture ◽  
Chronic Stable Angina ◽  
The Elderly ◽  
Developed Countries ◽  
Coronary Syndrome ◽  
Chronic Therapy ◽  
Artery Disease

Coronary atherosclerosis is a nearly universal finding in people over 75 years old living in developed countries, but is often sub-clinical. Broadly speaking, symptomatic patients manifest coronary artery disease in two distinct ways: chronic stable angina or an acute coronary syndrome. Stable angina produces symptoms of exertional chest pain due to fixed atherosclerotic narrowing of the coronary artery, and requires chronic therapy. In contrast, the acute coronary syndromes, namely acute myocardial infarction (MI) and unstable angina, occur as a result of plaque rupture or erosion leading to acute coronary arterial thrombosis and occlusion that requires emergency hospitalization and treatment.

scholarly journals Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability

2003 ◽  
Vol 178 (3) ◽  
pp. 373-380 ◽  
Author(s):  
CJ Malkin ◽  
PJ Pugh ◽  
RD Jones ◽  
TH Jones ◽  
KS Channer
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Protective Factor ◽  
Plaque Rupture ◽  
Thrombus Formation ◽  
Disease Process ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Clinical Consequences ◽  
Artery Disease

Inflammation plays a central pathogenic role in the initiation and progression of coronary atheroma and its clinical consequences. Cytokines are the mediators of cellular inflammation and promote local inflammation in the arterial wall, which may lead to vascular smooth muscle apoptosis, degradation of the fibrin cap and plaque rupture. Platelet adhesion and thrombus formation then occur, resulting clinically in unstable angina or myocardial infarction. Recent studies have suggested that cytokines are pathogenic, contributing directly to the disease process. 'Anti-cytokine' therapy may, therefore, be of benefit in preventing or slowing the progression of cardiovascular disease. Both oestrogens and testosterone have been shown to have immune-modulating effects; testosterone in particular appears to suppress activation of pro-inflammatory cytokines. Men with low testosterone levels are at increased risk of coronary artery disease. An anti-inflammatory effect of normal physiological levels of sex hormones may, therefore, be important in atheroprotection. In this Article, we discuss some of the mechanisms involved in atherosclerotic coronary artery disease and the putative link between testosterone deficiency and atheroma formation. We present the hypothesis that the immune-modulating properties of testosterone may be important in inhibiting atheroma formation and progression to acute coronary syndrome.

Study on Vitamin D deficiency in patients of diabetes mellitus presenting with Acute Coronary syndrome in a tertiary care hospital in South India

2020 ◽  
Vol 11 (5) ◽  
pp. 49-53
Author(s):  
Archana Bhat ◽  
Arunachalam Ramachandran ◽  
Pradeep Periera ◽  
Akshatha Rao Aroor
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Vitamin D ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Vitamin D Deficiency ◽  
Coronary Syndrome ◽  
Vitamin D Levels ◽  
Luminal Stenosis ◽  
Artery Disease

Background: Vitamin D, a fat-soluble vitamin has its receptor present in myriad of tissues and it modulates multiple cellular processes. Vitamin D deficiency is reported to be associated with coronary artery disease. Cardiovascular disease is the leading cause of mortality worldwide. Aims and Objective: The primary outcome was to investigate if there is a correlation of 25-OH levels with the percentage of luminal stenosis, as measured with coronary angiogram. The secondary outcome was to determine the differences in angiographically proven luminal stenosis across categories of 25-OH vitamin D levels. Materials and Methods: Thirty patients with acute coronary syndrome with diabetes mellitus were included in this cross-sectional descriptive study. All patients were tested for fasting vitamin D levels, fasting blood sugar, HbA1C and serum creatinine. Detailed history of the patients was recorded. Data was analyzed by the statistical software SPSS version 19 and p value <0.05 was considered significant. Statistical tests like Chi- square, independent t test and log regression was used. Results: In this study 30 patients undergoing coronary angiography for acute coronary syndrome, Vitamin D levels showed severe deficiency in 6.7% (2) cases while mild deficiency was seen in 50% of the cases. Patients with single vessel disease on the coronary angiogram had lower mean HbA1C (9.18) levels in our study. Patients with triple vessel disease had poorly controlled mean HbA1C levels (10.42). Conclusion: In this study we did not find any significant difference between the serum Vitamin D deficiency levels with patients with angiographic severity of the coronary artery disease. Patients with poorly controlled diabetes mellitus had more severe angiographic proven coronary artery disease.

scholarly journals Optimizing diagnosis of obstructive coronary artery disease by CT angiography: RCT's final results and 12-months follow-up

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.P Dias Ferreira Reis ◽  
R Ramos ◽  
P Modas Daniel ◽  
S Aguiar Rosa ◽  
L Almeida Morais ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Functional Test ◽  
Control Group ◽  
Diagnostic Strategy ◽  
Coronary Syndrome ◽  
Tertiary Center ◽  
Safety Endpoint ◽  
Artery Disease ◽  
Primary Safety Endpoint

Abstract Aim In patients (pts) with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) may improve pt selection for invasive coronary angiography (ICA) as alternative to functional testing. However. the role of CTA in symptomatic pts after abnormal functional test (FT) is incompletely defined. Methods and results This randomized clinical trial conducted in single academic tertiary center selected 218 symptomatic pts with mild to moderately abnormal FT referred to ICA to receive either the originally intended ICA (n=103) or CTA (n=115). CTA interpretation and subsequent care decisions were made by the clinical team. Pts with high risk features on FT, previous acute coronary syndrome, previously documented CAD, chronic kidney disease (GFR&lt;60ml/min/1.73m2) or persistent atrial fibrillation were excluded. The primary endpoint was the percentage of ICA with no significant obstructive CAD (no stenosis ≥50%) in each group. Diagnostic (DY) and revascularization (RY) yields of ICA in either group were also assessed. Pts were followed up for at least 1 year for the primary safety endpoint of all cause death/ nonfatal myocardial infarction/ stroke. Unplanned revascularization (UP) and symptomatic status (SS) were also evaluated. Pts averaged 68±9 years of age, 60% were male, 29% were diabetic. Nuclear perfusion stress test was used in 33.9% in CTA group and 31.1% in control group (p=0.655). Mean post (functional) test probability of obstructive CAD was 34%. Overall prevalence of obstructive CAD was 32.1%. In the CTA group, ICA was cancelled by referring physicians in 83 of the pts (72.2%) after receiving CTA results. For those undergoing ICA, non-obstructive CAD was found in 5 pts (15.6%) in the CTA-guided arm and 60 (58.3%) in the usual care arm (p&lt;0.001 Mean cumulative radiation exposure related to diagnostic work up was similar in both groups (6±14 vs 5±14mSv, p=0.152). Both DY (84.4% vs 41.7, p&lt;0.001) and RY (71.9% vs 38.8%, p=0.001) yields were significantly higher for CTA-guided ICA as compared to standard FT-guided ICA. The rate of the primary safety endpoint was similar between both groups (1.9% vs 0%, p=0.244), as well as the rates of UP (0.9% vs 0.9%, p=1.000) and SS (persistent angina: 29.6% vs 24.8%, p=0.425). Conclusions In pts with suspected CAD and mild to moderately abnormal ischemia test, a diagnostic strategy including CTA as gatekeeper is safe, effective and significantly improves diagnostic and revascularization yields of ICA. Funding Acknowledgement Type of funding source: None

Sign in / Sign up

Export Citation Format

Share Document