Abstracts LymphForsch 2/2015
Venous and non-venous origin of the lymphatic system in various murine organs
I. Martinez-Corral, M. Frye, T. Mäkinen
LymphForsch 2015; 19(2):76´81
Blood vessels form by means of two different processes, de novo formation of vessels from endothelial progenitors (vasculogenesis) and sprouting of vessels from pre-existing ones (angiogenesis). For a long time, it has been commonly thought that all lymphatic vessels are formed exclusively from veins through a sprouting process (lymphangiogenesis). Alternative non-venous progenitors of lymphatic endothelial cells (LECs) have been suggested in chicken and Xenopus tadpoles, but it is unclear whether they exist in mammals. With the aim of investigating the origin of the mammalian lymphatic vasculature, we performed genetic lineage tracing experiments and analyzed mutants lacking the Prox1 transcription factor, a master regulator of LEC identity, in Tie2 lineage venous-derived LECs. We show that, contrary to the current dogma, a significant part of dermal lymphatics forms independently of sprouting from veins. While lymphatic vessels of the cervical and thoracic skin develop via sprouting from venous-derived lymph sacs, vessels of lumbar and dorsal midline skin form via assembly of non-venous-derived cells into clusters and vessels through aprocess we refer to as „lymphvasculogenesis“. This process also takes place in the mesenteries.
However in this tissue, the non-venous source of LECs is the Tie2-positive hemogenic endothelium, which also gives rise to blood cells. Our results demonstrate the existence of different non-venous LEC progenitor populations, and help explain why lymphatic dysplasia may occur in only certain organs or locations. In addition, the existence of novel LEC progenitor cells may provide new strategies for the regenerative medicine of lymphatic vessels.
Keywords: mouse embryo, lymphangiogenesis, lymphvasculogenesis, mesenchyme, hemogenic endothelium
Cyclin-dependent kinase 5 – a new target in the lymphatic system
LymphForsch 2015; 19(2):82-83
Lymphatic disorders induce lymphedema and are involved in chronic inflammatory disorders. In order to develop strategies for treating these diseases, it is essential to understand the mechanisms that contribute to lymphatic dysfunction. We recently succeeded in identifying the central role of cyclin-dependent kinase 5 (Cdk5) during lymphatic development. Endothelial-specific deletion of Cdk5 leads to severe lymphedema and results in embryonic lethality. We traced this back to defects in lymphatic remodeling and valve formation. Our mechanistic studies showed that Cdk5 phosphorylates the forkhead transcription factor Foxc2 and regulates its transcriptional activity. In summary, our results identified the Cdk5-Foxc2 pathway as a central mechanism during lymphatic vessel development. This means that Cdk5 might be a potential target for diseases associated with lymphatic disorders.
Keywords: lymphatic vessel development, lymphangiogenesis, Cdk5, Foxc2
Heterogeneity of the origin of the lymphatic system
K. Mattonet, M. Jeltsch
LymphForsch 2015; 19(2):84-88
The question “How does the lymphatic system develop?” may be a simple one, but it is fundamental to our understanding of lymphatic malformations in children and the regeneration of lymphatics in adults. The question is by no means new and was already explored in the early 20th century. This resulted in a long-lasting controversy, which until recently had been far from being settled. The interest in the lymphatic system has greatly increased in recent years due to its implications in a variety of diseases. Several studies published this year address the heterogeneity of lymphatic endothelial cell development and unite previous controversially discussed data in a coherent model. These remarkable results, as well as the studies that paved their way, are discussed in this review.
Keywords: embryonic development, lymphatic system, lymphatic endothelial cells, lymphvasculogenesis, lymphangiogenesis, centrifugal, centripetal
Surgical treatment of morbid obesity and its sequelae
LymphForsch 2015; 19(2):89-91
Morbid obesity is increasing dramatically worldwide, significantly limiting life expectancy due to the associated comorbidities. Since purely conservative treatment measures offer limited chances of permanent and effective weight reduction, various surgical techniques have been developed. With these techniques, 80 % of overweight can be reduced, offering a means of permanently resolving morbid obesity.
Keywords: morbid obesity, metabolic surgery, gastric bypass
S. Pauli, B. Zoll, M. Zenker
LymphForsch 2015; 19(2):92-98
Noonan syndrome is a congenital disorder with an estimated prevalence of 1 in 1000-2500. The disorder is characterized by dysmorphic facial features, congenital heart defects, short stature, developmental delay, pectus deformities, hematological abnormalities and lymphatic disorders such as lymphedema. Noonan syndrome is also associated with a higher risk of myeloproliferative diseases such as juvenile myelomonocytic leukemia (JMML). Together with LEOPARD, Costello, cardiofacio-cutaneous (CFC) syndrome, neurofibromatosis type I and Legius syndromes, Noonan syndrome is classified as one of the „RASopathies“. The RASopathies are a clinically related group of developmental syndromes caused by genetic mutations that lead to an activation of the RAS signaling pathway. In this review, we describe the clinical aspects of Noonan syndrome and related disorders. We summarize the novel genes that have been reported to be associated with Noonan syndrome and highlight the pathophysiology and molecular aspects of this malformation syndrome.
Keywords: Noonan syndrome, rasopathy, RAS signalling pathway, lymphedema
Circumscribed pain on the amputation stump – Acroangiodermatitis of Mali
U. Wollina, B. Heinig
LymphForsch 2015; 19(2):99-101
Leg amputees commmonly experience pain sensations. The major differential diagnoses are stump pain and phantom pain. Pain can keep patients from wearing their prosthesis, which impairs rehabilitation and mobility. We report on a 52-year-old male patient who developed painful acroangiodermatitis of Mali after leg amputation. This disorder is a rare cause of pain in leg amputees. Consistent surgical treatment resulted in a pain-free situation that allowed the patient to continue rehabilitation. Differential diagnoses of the painful stump are discussed.
Keywords: stump pain, leg amputation, acroangiodematitis of Mali, surgery
Unusual cause of a thickened perimalleolar region in a patient with lymphedema: A case report
W. J. Brauer
LymphForsch 2015; 19(2):102-103
When diagnosing lymphedema, ultrasound is used mainly to detect interstitial fluid and secondary alterations of tissues including the lymph nodes, and to distinguish ambiguous localized swelling. It is also used to diagnose the triggers of secondary lymphedema. In this case of a patient with primary lymphedema, sonography revealed the proliferation of fatty tissue in the common sheath of the peroneal tendons, an unusual finding accompanied by a thickened perimalleolar region.
Keywords: lymphedema, liquid interstitial structures, sonography, perimalleolar region
Secondary lymphedema presenting as unilateral lipohypertrophy (non-pitting lymphedema): A case report
W. Schmeller, A. Baumgartner, Y. Frambach
LymphForsch 2015; 19(2):104-108
We present the case of non-pitting lymphedema without any clinically evident edema, but with manifestation of unilateral lipohypertrophy. Liposuction is the only effective treatment for this.
Keywords: non-pitting lymphedema, lipohypertrophy, liposuction