Human epicardium-derived cells reinforce cardiac sympathetic innervation

FWN – Publicaties zonder aanstelling Universiteit Leide

UNDERSTANDING LYMPHATIC DRAINAGE PATHWAYS OF THE OVARIES TO PREDICT SITES FOR SENTINEL NODES IN OVARIAN CANCER

Stem cells & developmental biolog

Pelvic lymphatic drainage pathways in relation to the autonomic nerves: implications for radical hysterectomy

Stem cells & developmental biolog

Lymphatic drainage pathways from the cervix uteri: Implications for radical hysterectomy?

Stem cells & developmental biolog

Nature and origin of the neointima in whole vessel wall organ culture of the human saphenous vein

Intimal proliferation is a characteristic feature of arteriosclerosis. Whole vessel wall organ culture systems have been developed to study the early stages of neointima formation. We have cultured a large number of explants of human saphenous vein specimens for several weeks, and have identified the nature of the cells in the newly formed intima by a panel of monoclonal antibodies recognizing endothelial cells (von Willebrand factor, platelet endothelial cell adhesion molecule-1 and EN-4 antigen), smooth muscle cells (monoclonal antibodies HHF35 and CGA-7) and fibroblasts (5B5 antibody). In addition we determined the uptake of fluorescently labelled acetylated low density lipoprotein by the surface cells of the explants. We found that an apparent neointima was formed in the vein organ system, the cells of which were predominantly smooth muscle cells and originated from the cut edges and from the adventitia of the vein segment. The endothelial cells originally lining the luminal surface of the vessel segments became overgrown by these cells. They remained at the base of the newly formed neointima and a number of them reorganized into capillary-like structures. Our data suggest that explant culture of saphenous vein does not reflect the classical concept of neointima formation, in which intimal smooth muscle cells migrate through the internal elastic lamina and accumulate in the intima. Although it has this limitation, the model may serve well to study specific aspects of cell migration, smooth muscle cell differentiation and angiogenesis, and may reflect aspects of intimal thickening at surgical suture sites

Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model

OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have carefully analyzed vascular remodeling in hypomorphic Pkd1 mouse model with dissecting aneurysms in the aorta. METHODS AND RESULTS - Quantitative real-time polymerase chain reaction revealed that in the aorta the expression of normal Pkd1 is reduced to approximately 26%. Using (immuno)histochemistry we have characterized the pathogenetic sequence for dissecting aneurysm formation. The aorta shows regions with accumulation of matrix components between the elastin lamellae. This is followed by increased numbers of smooth muscle cells and locally weakening of the media. In the intima, accumulation of matrix components and detachment of endothelial cells from the elastin lamellae results in a tear. The combination of weak media and a tear in the intima leads to rupture of the vessel wall resulting in intramural bleeding. CONCLUSIONS - The Pkd1 mouse reveals that polycystin1 is implicated in maintenance of the vessel wall structural integrity, and it is a useful model for dissecting aneurysm formation studies. © 2007 American Heart Association, Inc. Chemicals / CAS: calcium, 7440-70-2; collagen, 9007-34-5; elastin, 9007-58-3; fibronectin, 86088-83-7; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; osteopontin, 106441-73-0; perlecan, 143972-95-6; versican, 126968-45-4; polycystic kidney disease 1 protein; RNA, Messenger; TRPP Cation Channel

Understanding Lymphatic Drainage Pathways of the Ovaries to Predict Sites for Sentinel Nodes in Ovarian Cancer

Objective: In ovarian cancer, detection of sentinel nodes is an upcoming procedure. Perioperative determination of the patient’s sentinel node(s) might prevent a radical lymphadenectomy and associated morbidity. It is essential to understand the lymphatic drainage pathways of the ovaries, which are surprisingly up till now poorly investigated, to predict the anatomical regions where sentinel nodes can be found. We aimed to describe the lymphatic drainage pathways of the human ovaries including their compartmental fascia borders. Methods: A series of 3 human female fetuses and tissues samples from 1 human cadaveric specimen were studied. Immunohistochemical analysis was performed on paraffin-embedded transverse sections (8 or 10 µm) using antibodies against Lyve-1, S100, and [alpha]-smooth muscle actin to identify the lymphatic endothelium, Schwann, and smooth muscle cells, respectively. Three-dimensional reconstructions were created. Results: Two major and 1 minor lymphatic drainage pathways from the ovaries were detected. One pathway drained via the proper ligament of the ovaries (ovarian ligament) toward the lymph nodes in the obturator fossa and the internal iliac artery. Another pathway drained the ovaries via the suspensory ligament (infundibulopelvic ligament) toward the para-aortic and paracaval lymph nodes. A third minor pathway drained the ovaries via the round ligament to the inguinal lymph nodes. Lymph vessels draining the fallopian tube all followed the lymphatic drainage pathways of the ovaries. Conclusions: The lymphatic drainage pathways of the ovaries invariably run via the suspensory ligament (infundibulopelvic ligament) and the proper ligament of the ovaries (ovarian ligament), as well as through the round ligament of the uterus. Because ovarian cancer might spread lymphogenously via these routes, the sentinel node can be detected in the para-aortic and paracaval regions, obturator fossa and surrounding internal iliac arteries, and inguinal regions. These findings support the strategy of injecting tracers in both ovarian ligaments to identify sentinel nodes.Intelligent SystemsElectrical Engineering, Mathematics and Computer Scienc

Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life

OBJECTIVE - Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the murine vessel wall to accelerated development of cardiovascular disease in adult life. METHODS AND RESULTS - To investigate the epigenetic effect in utero, we generated genetically identical heterozygous apolipoprotein E-deficient progeny from mothers with a wild-type or apolipoprotein E-deficient background. A significant increase in loss of endothelial cell volume was observed in the carotid arteries of fetuses of apolipoprotein E-deficient mothers, but fatty streak formation was absent. Spontaneous atherosclerosis development was absent in the aorta and carotid arteries in adult life. We unilaterally placed a constrictive collar around the carotid artery to induce lesion formation. In offspring from apolipoprotein E-deficient mothers, collar placement resulted in severe neointima formation in 9 of 10 mice analyzed compared with only minor lesion volume (2 of 10) in the progeny of wild-type mothers. CONCLUSIONS - We conclude that the susceptibility to neointima formation of morphologically normal adult arteries is already imprinted during prenatal development and manifests itself in the presence of additional atherogenic risk factors in adult life. Future research will concentrate on the mechanisms involved in this priming process, as well as on prevention strategies. © 2007 American Heart Association, Inc