DYSFUNCTION OF THE VASCULAR ENDOTHELIUM AND THE DEVELOPMENT OF RENAL AND VASCULAR COMPLICATIONS IN DIABETES

2010 ◽  
pp. 197-222
Author(s):  
Coen D A Stehouwer
Keyword(s):  
Vascular Endothelium ◽  
Vascular Complications

scholarly journals Prospects in the treatment of diabetic nephropathy

2019 ◽  
Vol 43 (3) ◽  
pp. 20-22
Author(s):  
M. V. Shestakova ◽  
A. V. Vorontsov ◽  
S. G. Vykhristyuk ◽  
I. I. Dedov
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Angiotensin Converting Enzyme ◽  
Vascular Endothelium ◽  
Structural Changes ◽  
Vascular Complications ◽  
Converting Enzyme ◽  
Treatment And Prevention ◽  
Vasoactive Factors ◽  
Triggering Factor

The authors discuss new approaches to the treatment and prevention of diabetic nephropathy based on elimination of the pathogenetic factors of its development. Hyperglycemia, the main triggering factor of vascular complications of diabetes mellitus. induces a cascade of other pathological reactions, such as renal dysfunction, biochemical and structural changes in the basal membranes of renal capillaries, and stimulates the secretion of vasoactive factors of vascular endothelium and platelets. Blocking of these reactions by specific agents inhibits the progress of diabetic nephropathy. The authors share their experience gained in the treatment of diabetic nephropathy with inhibitors of angiotensin-converting enzyme, glycosaminoglycanes, and thromboxane synthesis inhibitors. These drugs are more effective if prescribed at the early stages of diabetic involvement of the kidneys.

Injury of Endothelium during the Cytostatic Therapy of AML Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3907-3907
Author(s):  
Alevtina Chervontseva ◽  
Valeri Savchenko ◽  
Yuri Romanov
Keyword(s):  
Vascular Endothelium ◽  
Mononuclear Cells ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Vascular Complications ◽  
Brdu Incorporation ◽  
Cytotoxic Action ◽  
Cytostatic Therapy ◽  
Healthy Donors ◽  
Cell Alterations

Abstract Background: At present, program chemotherapy represents the main approach to the treatment of patients with acute myeloid leukemia (AML). Chemotherapy is directed to the eradication of tumor clones and restoration of normal hematopoiesis. Using “7 + 3” protocol, including standard doses of cytosine arabinoside (ara-C) and daunorubicin (DNR) it is possible to obtain complete remission in 60–70% of patients. However, several vascular complications may take place during chemotherapy that could be related to vascular endothelium injury. Aims: To investigate the effects of ara-C and DNR on cultured human vascular endothelial cells (ECs) and to confirm endothelial injury by the detection of circulating ECs. Methods: Experiments were performed on cultured human umbilical vein ECs; cytostatic drugs were studied at therapeutical concentrations ranging from 1 ng/ml to 1 mg/ml. Effects were screened using phase-contrast microscopy, cell viability test, BRDU incorporation, immunocytochemistry, and flow cytometry. Results: At various concentrations, ara-C and DNR induced EC monolayer changes associated with either cytostatic or cytotoxic action. DNR provoked irreversible cell changes and monolayer damage; the action of ara-C leaded to elimination of mitotic ECs from self-renewing monolayer and to significant decrease of its density. Simultaneously, remaining ECs increased the expression of the cell adhesion molecules (P- and E-selectins, VCAM-1, ICAM-1, and PECAM-1) and enhanced their adhesiveness to blood mononuclear cells. Comparing the level of ECs circulating in peripheral blood of healthy donors and AML patients undergoing chemotherapy, we have find remarkable differences. In the studied group, the concentration of circulating ECs could be as high as 250–750 cells per 1 ml of blood. Conclusions: Obtained results allow to conclude that cytostatic therapy may cause systemic injury of the vascular endothelium related to functional cell alterations and/or massive EC loss.

scholarly journals Targeted polyelectrolyte complex micelles treat vascular complications in vivo

2021 ◽  
Vol 118 (50) ◽  
pp. e2114842118
Author(s):  
Zhengjie Zhou ◽  
Chih-Fan Yeh ◽  
Michael Mellas ◽  
Myung-Jin Oh ◽  
Jiayu Zhu ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Vascular Remodeling ◽  
Polyelectrolyte Complex ◽  
Vascular Complications ◽  
The United States ◽  
Therapeutic Effectiveness ◽  
Cell Adhesion Molecule 1 ◽  
Complex Micelles

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92aEC-TG/Apoe−/−) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe−/− mice. We tested the therapeutic effectiveness of the VCAM-1–targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1–targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti–miR-92a therapy in treating atherosclerosis and stenosis in Apoe−/− mice is markedly enhanced by the VCAM-1–targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.

EVIDENCE FOR AN INCREASED FIBRONECTIN SYNTHESIS IN VASCULAR ENDOTHELIUM OF DIABETIC SUBJECTS

1987 ◽  
Author(s):  
R Musso ◽  
A Longo ◽  
M L Morrone ◽  
R R Cacciola ◽  
A Lombardo ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelium ◽  
Plasma Levels ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Type Ii ◽  
Before And After ◽  
Baseline Values ◽  
Normal Controls ◽  
Commercial Kit

Increased plasma levels of Fibronectin (Fn),a well known adesive glycoprotein synthesized in vessel endothelial cells, have been reported in diabetes mellitus (DM). Previously, we provided evidence that in type II DM an elevated storage of Fn is present in endothelial cells. We here report that in diabetic subjects an abnormal synthesis of Fn in endothelial cells could also occur. To verify this hypothesis, in 15 patients affected by type II DM, age ranging 36-59, of both sex, without overt clinical vascular complications and in glycometabolic compensation (Hb Alc 8.9 ± 1.5) we evaluated before and after venostasis repeated at several times 30, 60, 90,180 and 210 min the Fn plasma levels. Five healthy volunteers, age and sex comparaf-h ble, were utilized as normal controls. The venostasis were performed at forearm pressure of 10 mmHg over diastolic x 20 min and blood samples were collected from the same vein at the intervals above indicated. Plasma Fn was evaluated by ELISA immuno-enzymatic tecnique using a commercial kit (Biochemia, Milan). The diabetic patients showed after the first venostasis a significant (p<0.001) increase of Fn (317 ± 103μg/ml) versus the baseline values (225±79 μg/ml)while normal controls did not (before 103 ± 37, after 139±61). Such an increase was also seen in EM after the second venostasis ( 298 ±91 μg/ml, vs 128±58 in controls), whereas at third venostasis plasma Fn levels retoumed to the values comparable to the basal ones both in diabetics (245 ±. 88 μg/ml) and in controls (93±41 μg/ml). After 90 min pause by performing the fourth venostasis we observed in diabetics a further increase pf Fn (298±131μg/ml) which reached:again the values noted after the first. No change, on the contrary,was found in the normal group (95±21). In the last venostasis,carried out 30min from the fourth, the plasna Fn lasted significantly (p<0.001.) increased in diabetics (281±107 μg/ml) respect to normal controls (102±19 μg/ml).Our data, therefore, would suggest that in vascular endothelium cf type II DM an increased synthesis of Fn occurs as well.

V1157: Vascular Complications in Laparoscopic Urologic Procedures

2005 ◽  
Vol 173 (4S) ◽  
pp. 314-314
Author(s):  
Mirandolino B. Mariano ◽  
Rene J. Sotelo ◽  
Flavia Santinelli ◽  
Alejandro J. Garcia ◽  
Antonio Finelli ◽  
...  
Keyword(s):  
Vascular Complications
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