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Biomedical subjects

Hannes Gaenzer

Publications and source records attributed to Hannes Gaenzer.

8 recordsLinked to original sources

The neuropeptide secretoneurin acts as a direct angiogenic cytokine in vitro and in vivo.

BACKGROUND: Secretoneurin is an abundant neuropeptide of the central, peripheral, and autonomic nervous systems, located in nerve fibers characterized by a close interaction with blood vessels and known to stimulate endothelial cell migration. METHODS AND RESULTS: We hypothesized that secretoneurin might act as an angiogenic cytokine and tested for these effects in vivo using a mouse cornea neovascularization model and in vitro by assessing capillary tube formation in a matrigel assay. In vivo, secretoneurin-induced neovasculature is characterized by a distinct pattern of arterial and venous vessels of large diameter and length. Immunohistochemical staining for CD-31 revealed endothelial lining of the inner surface of these vessels, and recruitment of alpha-smooth muscle actin-positive perivascular cells suggests vessel maturation. In vitro, secretoneurin-induced capillary tube formation was dose dependent and specific, confirming that effects of secretoneurin occur directly on endothelial cells. Secretoneurin also stimulated proliferation and exerted antiapoptotic effects on endothelial cells and activated intracellular phosphatidylinositol 3' kinase/Akt and mitogen-activated protein kinase pathways, as demonstrated by increased phosphorylation of Akt and extracellular signal-regulated kinase. CONCLUSIONS: These data show that secretoneurin represents a novel direct angiogenic cytokine and reiterate the coordinated relationship between nervous and vascular systems.

Angiogenesis Inducing Agents↗

Unsuspected mesenteric vein thrombosis in a patient with a hereditary bleeding disorder.

We report on a female patient with hereditary hemorrhagic teleangiectasia complicated by subacute thrombosis of the superior mesenteric vein. Despite gastrointestinal bleeding, anticoagulation therapy with heparin had to be performed to prevent bowel infarction. In this case, local vascular lesions with altered blood flow in combination with hyperfibrinogenemia might have caused superior mesenteric vein thrombosis.

Blood Coagulation Disorders, Inherited↗

Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis.

OBJECTIVES: We studied associations between iron status and early functional and structural vascular abnormalities in patients with hereditary hemochromatosis (HH). BACKGROUND: Iron may be involved in atherogenesis, and patients bearing a genetic mutation associated with HH are possibly at risk of developing coronary heart disease. METHODS: We studied the vascular properties of 41 HH patients who had homozygosity for the C282Y mutation, along with 51 age-matched control subjects, by determination of endothelium-dependent dilation (EDD) of the brachial artery and intima-media thickness (IMT) of the carotid artery. RESULTS: Male HH patients who were not receiving phlebotomy therapy showed a reduced EDD and increased IMT compared with controls and HH patients receiving therapy. In female HH patients, irrespective of treatment status, vascular parameters were not different from those of controls, and none of these patients had severe iron overload. In HH patients, increased iron load was significantly associated with reduced EDD and increased IMT. Moreover, we found a positive correlation between body iron stores and indicators of oxidative stress. When previously untreated male HH patients were re-investigated after intensive phlebotomy therapy, a significant improvement in EDD was observed (2.6 +/- 1.3% before vs. 5.5 +/- 2.1% after treatment, p = 0.0015). CONCLUSIONS: Impaired endothelial function and increased IMT are associated with iron overload, with subsequent induction of oxidative stress, and are not linked to a genetic disability in HH patients. Consequent iron-depletion therapy normalizes endothelial function and may thus reduce the increased risk of cardiovascular events. Female patients may be at a reduced risk, presumably due to continuous iron loss by menstruation.

Adult↗

Effect of insulin therapy on endothelium-dependent dilation in type 2 diabetes mellitus.

Endothelial dysfunction is an early marker of atherosclerosis occurring in patients with type 2 diabetes mellitus. Endothelium-dependent dilation (EDD) has been shown to improve by combined therapy of insulin and metformin. Studies on endothelium-independent vasodilatory capacity, however, have had controversial results. We sought to investigate the vascular reactivity--EDD and endothelium-independent dilation--and their changes induced by the addition of insulin therapy to patients with type 2 diabetes mellitus pretreated with diet and oral hypoglycemic drugs. We therefore performed vascular studies in 21 poorly controlled type 2 diabetic patients and 11 nondiabetic control subjects by using high resolution ultrasound of the brachial artery. After 3 months of additional insulin therapy, vascular and laboratory measurements including C-reactive protein and parameters of glucose and lipoprotein metabolism were repeated. At baseline, EDD was significantly impaired in diabetic patients compared with controls (2.7 +/- 2.2% vs 7.0 +/- 1.8%, p <0.001), whereas endothelium-independent dilation was normal in both groups. After insulin therapy, EDD increased from 2.7 +/- 2.2% to 5.0 +/- 2.8% (p <0.001) in diabetic patients. All other vascular parameters did not change over the treatment period. The absolute change in EDD showed a significant negative correlation with the change in hemoglobin A(1c) (r = -0.67, p <0.001) and with fasting blood glucose (r = -0.84, p <0.001) levels. In contrast, there was no correlation between EDD and the observed changes in lipid and C-reactive protein levels. Our findings demonstrate that insulin therapy has beneficial effects on vascular function, resulting in enhanced EDD, most probably due to an improved glycemic control as the underlying mechanism.

Adult↗

Splanchnic blood flow determination in patients with suspected chronic intestinal ischaemia.

Chronic intestinal ischaemia is characterized by postprandial abdominal pain and prominent weight loss, often leading to the first clinical suspicion of malignancy. After ruling out various gastrointestinal disorders, chronic intestinal ischaemia should be considered as a potential diagnosis. Besides the clinical picture, various non-invasive procedures are helpful in establishing the diagnosis. Whereas a plain abdominal radiography may show arterial calcifications, duplex ultrasonography is nowadays the leading diagnostic procedure for ruling out significant disease. Another promising and increasingly used technology is magnetic resonance angiography. Suspicious findings must be followed by the gold standard in diagnosis, namely splanchnic angiography. Since all these technologies provide only anatomical evidence of disease, functional imaging techniques assessing splanchnic blood flow after meal challenge using the invasive indocyanine green method may be helpful. However, further studies are needed in the use of this experimental technique in the workup of these patients.

Abdominal Pain↗