Background: Allograft coronary vasculopathy results from a complex interplay between immunologic and non-immunologic factors. We devised a computerized biopsy scoring method based on histopathology to predict the development of coronary vasculopathy.
Methods: One hundred forty heart transplant recipients underwent serial intravascular ultrasound analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for development of coronary vasculopathy (change in coronary maximal intimal thickness, CMIT). We evaluated serial endomyocardial biopsy specimens for cellular rejection, vascular rejection, ischemia, and fibrosis. In a mathematical model, we computed a biopsy score in each patient based on the duration and severity of histopathology.
Results: We found a significant correlation between biopsy score (RY) and progression of coronary vasculopathy (r = 0.54, p = 0.001). Using a sensitivity analysis method, an RY value of > or =560 predicted development of coronary vasculopathy with a sensitivity of 86%, specificity of 62%, and diagnostic accuracy of 80%. Compared with patients with low-risk biopsy scores (RY < 560, n = 37), patients with high-risk biopsy scores (RY > or = 560, n = 103) had increased progression of coronary vasculopathy (CMIT, 0.59 +/- 0.29 vs 0.19 +/- 0.10 mm, p < 0.001) and worse 7-year event-free survival (60% vs 91%, p = 0.01).
Conclusion: The biopsy score is an effective method for predicting the development of coronary vasculopathy and for predicting outcome in cardiac transplant recipients.
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http://dx.doi.org/10.1016/s1053-2498(02)00415-1 | DOI Listing |
Molecules
December 2024
Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia.
Wnt (wingless-type MMTV integration site family) signaling is an evolutionary conserved system highly active during embryogenesis, but in adult hearts has low activities under normal conditions. It is essential for a variety of physiological processes including stem cell regeneration, proliferation, migration, cell polarity, and morphogenesis, thereby ensuring homeostasis and regeneration of cardiac tissue. Its dysregulation and excessive activation during pathological conditions leads to morphological and functional changes in the heart resulting in impaired myocardial regeneration under pathological conditions such as myocardial infarction, heart failure, and coronary artery disease.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Pittsburgh Heart, Lung and Blood Vascular Medicine Institute (VMI), University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Matrix metalloproteinase-2 (MMP-2), a zinc-dependent enzyme, plays a critical role in the degradation and remodeling of the extracellular matrix (ECM). As a member of the gelatinase subgroup of matrix metalloproteinases, MMP-2 is involved in a variety of physiological processes, including tissue repair, wound healing, angiogenesis, and embryogenesis. It is primarily responsible for the degradation of type IV and V collagen, fibronectin, laminin, and elastin, which are essential components of the ECM.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Hutchinson-Gilford progeria syndrome (HGPS) is a pediatric condition characterized by clinical features that resemble accelerated aging. The abnormal accumulation of a toxic form of the lamin A protein known as progerin disrupts cellular functions, leading to various complications, including growth retardation, loss of subcutaneous fat, abnormal skin, alopecia, osteoporosis, and progressive joint contractures. Death primarily occurs as the result of complications from progressive atherosclerosis, especially from cardiac disease, such as myocardial infarction or heart failure, or cerebrovascular disease like stroke.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Centre for Heart Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia.
Programmed cell death, especially programmed necrosis such as necroptosis, ferroptosis, and pyroptosis, has attracted significant attention recently. Traditionally, necrosis was thought to occur accidentally without signaling pathways, but recent discoveries have revealed that molecular pathways regulate certain forms of necrosis, similar to apoptosis. Accumulating evidence indicates that programmed necrosis is involved in the development of various diseases, including myocardial ischemia-reperfusion injury (MIRI).
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Experimental Immunology, Medical University of Lublin, Chodźki 4a Street, 20-093 Lublin, Poland.
Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary vascular resistance and right heart failure, with emerging evidence suggesting a key role for immune dysregulation in its pathogenesis. This study aimed to assess the involvement of lymphocytes, particularly regulatory T cells (Tregs), and the expression of immune checkpoint molecules PD-1 and PD-L1 on peripheral blood subpopulations in patients diagnosed with PAH. The study involved 25 patients; peripheral blood mononuclear cells were isolated and subsequently analyzed using flow cytometry to quantify the Treg cell percentage and evaluate PD-1 and PD-L1 expression across the T and B cells.
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