Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria.
Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.
Gasic
S
S
Department of Internal Medicine III, University Hospital of Vienna, Wien, Austria.
Wagner
O F
OF
Fasching
P
P
Ludwig
C
C
Veitl
M
M
Kapiotis
S
S
Jilma
B
B
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D019040:E-Selectin / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D017328:Fosinopril / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000097:blood; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood* / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D001786:Blood Glucose; D019040:E-Selectin; D017328:Fosinopril; D006442:Glycated Hemoglobin; D018799:Intercellular Adhesion Molecule-1; D007703:Peptidyl-Dipeptidase A; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D019010:Vascular Cell Adhesion Molecule-1