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Morphometric and immunocytochemical analysis of coronary arterioles in human transplanted hearts
A T Armstrong1, A R Strauch, A Kardan
1Department of Internal Medicine, Ohio State University College of Medicine, Columbus, USA.
Insights
Heart transplant recipients
Area of Science:
- Cardiovascular Research
- Transplantation Immunology
- Vascular Biology
Background:
- Heart transplant vascular sclerosis affects epicardial coronaries.
- Coronary arterioles (<100 microns) in heart transplant recipients were analyzed for disease.
- Previous studies focused on larger epicardial vessels, leaving microvasculature disease less understood.
Purpose of the Study:
- To investigate the presence and characteristics of disease in coronary arterioles of heart transplant recipients.
- To assess changes in arterioles over time post-transplantation.
- To compare arterioles from transplanted hearts to non-diseased controls.
Main Methods:
- Quantified stenosis in 164 arterioles from 30 transplant recipients using computer imaging.
- Grouped arterioles into early (0-6 months), middle (6-18 months), and late (18-36 months) post-transplant periods.
- Utilized immunohistochemistry for proliferating cell nuclear antigen (PCNA) and alpha-actin to assess cellular proliferation and smooth muscle content.
Main Results:
- No significant difference in stenosis percentage was observed between transplanted and control groups.
- Proliferating cell nuclear antigen (PCNA) antibody binding was not detected in any transplanted group.
- Increased smooth muscle alpha-actin was significantly higher in late-stage transplant groups compared to early and middle stages.
Conclusions:
- Coronary microvasculature in transplanted hearts shows no intimal thickening or cellular proliferation within 3 years.
- Vascular remodeling, indicated by increased smooth muscle alpha-actin, may occur in response to injury-related cytokines.
- These findings highlight potential microvascular changes beyond traditional sclerosis in heart transplantation.
Background:
Heart transplant vascular sclerosis has been characterized in epicardial coronaries of human transplanted hearts. The purpose of this study was to analyze coronary arterioles (< 100 microns in diameter) within endomyocardial biopsy specimens from heart transplant recipients for the presence of disease.
Methods:
The morphologic compartments of trichrome-stained vessels were quantified by means of computer imaging to measure the percentage of stenosis of 164 arterioles from 30 transplant recipients over time. The arterioles were divided into three groups based on their biopsy date after transplantation: early (0 to 6 months), middle (6 to 18 months), and late (18 to 36 months). The percentage of stenosis of arterioles from a control group of nondiseased hearts was compared with the grafts. Also, arterioles from heart transplant recipients were immunohistochemically labeled with an antibody, PC10, specific for proliferating cell nuclear antigen. The arterioles were immunocytochemically labeled with an antibody specific for vascular smooth muscle alpha-actin and the fluorescent signal was analyzed.
Results:
The percentage of stenosis was not significantly different among the early, middle, late, and control groups. Vessels from the early, middle, and late groups did not show binding of the PCNA antibody. The antibody signal intensity and amount of alpha-actin within each vessel was significantly higher in the late groups as compared with the early and middle groups.
Conclusions:
The coronary microvasculature of human transplanted hearts does not exhibit intimal thickening or cellular proliferation within 3 years after transplantation. However, as shown by an increase of smooth muscle alpha-actin over time, vascular remodeling may occur in response to cytokines released as a result of injury.