Search

Aims: Coronary thrombotic occlusion in ST-segment elevation myocardial infarction (STEMI) patients is often preceded by episodes of progressive growth of the thrombus mass. Similar to wound healing, the organization of thrombus could depend on ingrowth of microvessels in order to stabilize its structure. We investigated the patterns of neovascularization in different stages of coronary thrombus evolution., Material and Methods: Thrombectomy materials obtained from STEMI patients were histologically classified according to thrombus age in three groups: fresh (< 1 day), lytic (1-5 days) or organized (> 5 days) thrombi. Forty thrombi of each group were randomly collected. Neovascularization in the thrombi was evaluated histomorphologically and with immunodouble stains to visualize various differentiation antigens of endothelial cells (ECs) and primitive cells., Results: Morphologically, ECs in the coronary thrombi manifested as: single cells, cell clusters or microvessels. CD31+/CD34+ ECs were present in 98% of all the thrombi. In addition, endothelial clusters were found in 63% of the fresh thrombi (< 1 day). CD105+, Ki67+, or C-kit+ ECs (active, proliferating cells) were observed in all the stages, but significantly more in organized thrombi (> 5 days) compared with fresh and lytic ones (< 5 days), and mainly as cell clusters (P ≤ 0.05 for all). CD133+ primitive cells were found only sporadically in 11% of all the samples., Conclusion: EC proliferation is initiated very early, and gradually progresses during the organization process of thrombus after coronary plaque disruption, with only a limited contribution of primitive cells in this process., (© 2012 International Society on Thrombosis and Haemostasis.)

Aims: To study the time relationship between the onset of coronary thrombosis and sudden unexpected cardiac death in young adults., Methods and Results: Hearts of 11 young adults (< or = 35 years), who had died within 1h after onset of symptoms and presented with a coronary thrombotic occlusion were studied retrospectively for the type of underlying plaque complication and the time of onset of thrombus formation. In all cases tissue blocks were taken from the occluded artery and sectioned for microscopic evaluation. Of 11 culprit lesions 10 were mainly fibrocellular; only one was lipid-rich. Inflammatory cells were found in all plaques, albeit in highly variable amounts. Plaque erosion had occurred in nine; deep ruptures in two. Analysis of the plaque-related occluding thrombus revealed fresh thrombosis in three (both ruptured plaques and one erosion); the other eight, however, showed occlusion with different histological stages of organization of thrombus., Conclusions: Despite strict inclusion criteria for sudden death in these young adults, the majority must have had plaque instability for some time, since thrombus formation had occurred at least days to weeks prior to the acute event., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Objective: To discriminate between chronic inflammation and acute activation of the plaque immune response in culprit lesions of patients with acute coronary syndromes., Design: Retrospective study., Setting: Tertiary referral centre., Subjects: 71 patients having coronary atherectomy were classified according to their ischaemic syndrome: stable angina (n = 23); stabilised unstable angina (n = 18); refractory unstable angina (n = 11); and acute myocardial infarction (n = 19)., Main Outcome Measures: Immunohistochemical measurement of interleukin 2 receptor (IL-2R) (CD25) positive cells expressed as a percentage of the total amount of (CD3 positive) T lymphocytes in frozen sections of atherectomy specimens., Results: The number of lesions containing IL-2R (CD25) positive T cells increased with severity of the ischaemic coronary syndrome (stable angina, 52%; stabilised unstable angina, 77.8%; refractory unstable angina, 90.9%; acute myocardial infarction, 89.4%). The percentage of activated T cells (CD25/CD3 ratios x100) increased in lesions associated with refractory unstable angina (7.8%) and acute myocardial infarction (18.5%), compared with those in lesions associated with either chronic stable angina (2.2%) or stabilised unstable angina (3.3%)., Conclusions: An increase in the percentage of IL-2R positive T lymphocytes in culprit lesions of patients with acute coronary syndromes indicates recent activation and amplification of the immune response within plaques. This may result in a burst of inflammatory products with tissue degrading and vasoactive properties and, hence, could initiate or accelerate the onset of an acute coronary event.

Background: C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family and is considered to have regulatory effects on vascular tone and smooth muscle growth. Since these features play a role in atherogenesis, the presence of CNP at such sites was studied., Methods and Results: Thirty-three coronary artery segments were harvested at autopsy: 10 normal, with diffuse intimal thickening, and 23 atherosclerotic lesions. Samples were snap-frozen and processed for immunohistochemical staining. For the identification of CNP, a mouse monoclonal antibody (KY-CNP-1) was used. 1A4, EBM-11 (CD68), and von Willebrand factor antibodies were used to stain smooth muscle cells, macrophages, and endothelial cells, respectively. CNP is present in several cell types. Normal arterial segments show CNP-positive endothelial cells. Hypercellular atherosclerotic lesions show distinct CNP positivity of smooth muscle cells and macrophages but a decrease in positivity of endothelial cells. Advanced atherosclerotic lesions contain CNP-positive macrophages, but the smooth muscle cells within the fibrous cap and the surface endothelial cells are almost all CNP-negative., Conclusions: These observations suggest that CNP has functional significance in atherogenesis.

Objective: To investigate the extent of plaque inflammation in culprit lesions of patients with chronic stable angina., Design: Retrospective study., Setting: Amsterdam reference centre., Subjects: 89 consecutive patients who underwent directional coronary atherectomy, 58 of whom met the following inclusion criteria: chronic stable angina (Canadian Cardiovascular Society classification 1-3 (group 1, n = 28)); unstable angina (Braunwald class II (group 2, n = 18)); unstable angina (Braunwald class III (group 3, n = 12))., Interventions: Directional atherectomy in patients with angina pectoris., Main Outcome Measures: Tissue areas of culprit lesions occupied by inflammatory cells and smooth muscle cells related to clinically defined ischaemic syndrome., Results: Areas (% of total surface area (mean (SEM)) rich in smooth muscle cells were larger in patients with chronic stable angina (group 1, 51.2 (20.9)) than in those with unstable angina (group 2, 42.1 (20.5); group 3, 29.5 (19.4)) (1 v 2 and 2 v 3, NS; 1 v 3, P < 0.004). Macrophage rich areas were significantly smaller in patients with stable angina (group 1, 21.8 (11.9)) than in those with unstable angina (group 2, 31.5 (14.6); group 3, 46.4 (16.7)) (1 v 2, P < 0.02; 2 v 3, P < 0.02; 1 v 3, P < 0.001). Mean numbers of T cells per mm2 were as follows: group 1, 17 (9.4); group 2, 25 (15.9); group 3, 41 (30.6) (1 v 2, P 0.04; 2 v 3, P 0.07; 1 v 3, P < 0.001). Areas with HLA-DR positive cells showed the same pattern as macrophages and T cells and were smaller in stable (29.9 (12.4)) than in unstable angina (group 2, 40.4 (17.6); group 3, 52.4 (12.0)) (1 v 2, P < 0.02; 2 v 3, P < 0.05; 1 v 3, P < 0.001)., Conclusion: The inverse relation between the extent of inflammatory activity in plaque tissues of culprit lesions and the clinical stability of the ischaemic syndrome supports the concept that reduction of inflammation favours plaque stabilisation. At the same time, the considerable overlap between groups indicates that patients with clinically stable angina do not all have histologically stable plaques.

Objective: To evaluate whether expression of platelet derived growth factor B (PDGF-B) protein is associated with expression of its receptor protein in human coronary arteries after angioplasty and to identify cells involved., Background: PDGF is considered an important growth factor in the repair process of the vessel wall after angioplasty. In situ hybridisation has revealed expression of PDGF-A and -B chain messenger ribonucleic acid (mRNA) in human coronary arteries at sites of postangioplasty injury., Methods: Target and non-target sites of eight coronary arteries were studied immunohistochemically for PDGF-B and PDGF-beta receptor proteins in relation to macrophages, T lymphocytes, smooth muscle cells, and HLA-DR positive cells., Results: The PDGF-B and PDGF-beta receptor proteins were expressed in areas with distinct repair, containing alpha actin negative spindle cells, macrophages and, at later stages, alpha actin positive smooth muscle cells as well. When the neointima was composed mainly of alpha actin smooth muscle cells, PDGF-B expression was rare and PDGF-beta receptor expression was negative., Conclusions: There is expression of PDGF-B and PDGF-beta receptor proteins at sites of postangioplasty repair in human coronary arteries. The associated cells are mainly macrophages and alpha actin negative spindle cells; the latter may be dedifferentiated smooth muscle cells. A link between PDGF expression and the postangioplasty time interval suggests a relation with cell differentiation as part of the maturation of the repair tissue. Mutual expression of both the growth factor and its receptor protein strongly suggests that in humans a PDGF mediated repair process occurs, with involvement of smooth muscle cells and macrophages.

Background: The study was designed to verify the concept of plaques "at risk" and whether inflammation could play a role in plaque rupture and thrombosis., Methods and Results: In 20 patients who had died of acute myocardial infarction, the thrombosed coronary artery was identified and the site of plaque rupture was traced in serial sections. The cellular characteristics of the fibrous cap at the immediate site of rupture were analyzed and compared with the adjacent cap tissue by use of monoclonal antibodies reactive with macrophages, T lymphocytes, and smooth muscle cells. A deep intimal rupture, extending into the lipid core, was encountered in 12 plaques, whereas 8 had superficial erosions only. Ten atherosclerotic plaques had a distinctly attenuated fibrous cap covering a large atheroma, 7 showed a thick fibrocellular cap overlying a lipid pool, and 3 showed a fibrocellular lesion without a clear lipid core. Macrophages, and to a lesser extent T lymphocytes, were the dominant cells at the immediate site of either rupture or superficial erosion in each instance. These sites, moreover, were always characterized by abundant expression of HLA-DR antigens on both inflammatory cells and adjacent smooth muscle cells, suggesting an active inflammatory reaction. In terms of overall cellular composition of the ruptured plaques, the dominant cell types were macrophages and T cells in 11, smooth muscle cells in 3, and mixtures of both in 6., Conclusions: The underlying atherosclerotic plaque morphology in complicated coronary artery lesions causing acute myocardial infarction is heterogeneous with respect to both plaque architecture and cellular composition. However, the immediate site of plaque rupture or erosion is always marked by an inflammatory process. This suggests that inflammation plays a role in destabilizing the fibrous cap tissue and, thus, in enhancing the risk of coronary thrombosis.