Morphological and quantitative changes of the initial myocardial lymphatics in terminal heart failure.
ABSTRACT Terminal heart failure is associated with chronic myocardial edema, which in part is compensated by increased myocardial lymph flow. However, little is known about the impact of terminal heart failure on lymphangiogenesis. The purpose of the study was to investigate the morphological and quantitative changes of the initial myocardial lymphatics in terminal heart failure.
Paraffin-embedded left ventricular endomyocardial biopsies, taken during heart transplantation from 7 heart transplant recipients (failing heart) and 8 heart transplant donors (control), were investigated by immunohistostaining and triple immunofluorescence for lymphatic endothelial markers LYVE-1, PROX-1, and VEGFR-3. The vessel density was calculated and the ratio of open versus collapsed vessels was estimated by analyzing randomly selected marked vessels.
The absolute densities of lymph vessels in failing and control myocardium were not significantly different for all investigated markers. The ratio of open LYVE-1 positive lymph vessels in failing heart was significantly higher than in control (64+/-12.5 vs. 44.3+/-9.3, p<0.008). There was no difference for the ratio of open VEGFR-3 vessels between groups (69.0+/-17.5 vs. 70.7+/-17.2). Triple fluorescent immunohistostaining revealed in failing hearts LYVE-1 and PROX-1 positive open vessels, which were VEGFR-3 negative. VEGFR-3 positive, but LYVE-1 and PROX-1 negative vessels could also be seen.
Myocardial initial lymphatics in patients with terminal heart failure undergo significant morphological changes in comparison to normal hearts. The ratio of open LYVE-1 vessels was higher in failing hearts by no difference in absolute densities for all markers. These findings suggest that appositional growth of initial lymphatics, rather than "de novo" genesis from pluripotent stem cells or sprouting from preexisting venous vessels, may be the predominant mechanism of lymphangiogenesis in terminal heart failure.
Article: Inflammatory lymphangiogenesis in a rat transplant model of interstitial fibrosis and tubular atrophy.[show abstract] [hide abstract]
ABSTRACT: We have previously reported de novo lymphangiogenesis in human renal allograft nephrectomy specimens that exhibited interstitial fibrosis and tubular atrophy (IFTA). This study examined whether a similar pathology developed in an experimental model of renal transplantation in the rat. Renal transplants were carried out in rats comprising both isografts (Lewis kidneys → Lewis rats) and allografts (Fisher kidneys → Lewis rats). Animals were immunosuppressed in the immediate postoperative period and sacrificed at 12 months. Experimental readouts included lymphatic vessel number and location, inflammatory cell infiltration, interstitial fibrosis, renal function, blood pressure and proteinuria. Rat allografts demonstrated the characteristic features of IFTA with increased macrophage and T cell infiltration and scattered B cells aggregates. Rat allografts exhibited impaired renal function and proteinuria. Although there was no difference in the number of perivascular lymphatic vessels, there was a striking 18-fold increase in the number of interstitial lymphatic vessels in renal allografts. Furthermore, the lymphatic vessel number correlated with the extent of interstitial fibrosis. This rat allograft model of IFTA demonstrates a marked increase in the number of interstitial lymphatic vessels and mirrors previous work in failing human renal allografts.Transplant International 04/2012; 25(7):792-800. · 2.92 Impact Factor