endothelin-1 and Aortic-Aneurysm

This review discusses the role of biomarkers for both diagnoses and disease monitoring before, during, and after treatment of aortic dissection.

Topics: Aortic Aneurysm; Aortic Dissection; Biomarkers; C-Reactive Protein; Calcium-Binding Proteins; Calponins; Elastin; Endothelin-1; Fibrin Fibrinogen Degradation Products; Humans; Microfilament Proteins; Natriuretic Peptide, Brain; Peptide Fragments; Peptidyl-Dipeptidase A; Receptors, Notch; Smooth Muscle Myosins; Transforming Growth Factor beta

Because both endothelin-1 (ET-1) and angiotensin II (AngII) are independent mediators of arterial remodeling, we sought to determine the role of ET receptor inhibition in AngII-accelerated atherosclerosis and aortic aneurysm formation. We administered saline or AngII and/or bosentan, an endothelin receptor antagonist (ERA) for 7, 14, or 28 days to 6-week- and 6-month-old apolipoprotein E-knockout mice. AngII treatment increased aortic atherosclerosis, which was reduced by ERA. ET-1 immunostaining was localized to macrophage-rich regions in aneurysmal vessels. ERA did not prevent AngII-induced aneurysm formation but instead may have increased aneurysm incidence. In AngII-treated animals with aneurysms, ERA had a profound effect on the non-aneurysmal thoracic aorta via increasing wall thickness, collagen/elastin ratio, wall stiffness, and viscous responses. These observations were confirmed in acute in vitro collagen sheet production models in which ERA inhibited AngII's dose-dependent effect on collagen type 1 α 1 (COL1A1) gene transcription. However, chronic treatment reduced matrix metalloproteinase 2 mRNA expression but enhanced COL3A1, tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2 mRNA expressions. These data confirm a role for the ET system in AngII-accelerated atherosclerosis but suggest that ERA therapy is not protective against the formation of AngII-induced aneurysms and can paradoxically stimulate a chronic arterial matrix remodeling response.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Aorta; Aortic Aneurysm; Apolipoproteins E; Atherosclerosis; Biomechanical Phenomena; Bosentan; Cardiovascular Agents; Cell Adhesion; Collagen; Down-Regulation; Endothelin-1; Integrin beta1; Interferon-gamma; Mice; Mice, Knockout; Stress, Physiological; Sulfonamides; Vasoconstrictor Agents

Endothelin-1 (ET-1) and B-type natriuretic peptide (BNP) have been reported to be involved in numerous cardiovascular diseases. The study aim was to monitor the circulating plasma levels of these peptides in patients affected by aortic disease, and to identify any changes in such levels after surgical treatment.. A total of 81 patients (52 males, 29 females; mean age 64 +/- 11 years) with aortic disease underwent surgery. The conditions included aortic valve stenosis (n=36), aortic valve regurgitation (n=11), ascending aortic aneurysm (n=6), and combined ascending aortic aneurysm and valvulopathy (n=28). Circulating plasma levels of ET-1 and BNP were measured in all patients before and at 12 months after surgery.. Compared to the preoperative situation, significant decreases were found postoperatively in plasma levels of ET-1 (4.2 +/- 0.1 versus 3.1 +/- 0.1 pM; p < 0.001) and BNP (0.071 versus 0.017 ng/ml; p < 0.001), combined with an increased cardiac function and decreased ventricular dimensions. The preoperative levels of both peptides were similar in all patient groups, and were decreased to a similar extent regardless of the diagnosis. Basal levels of ET-1 were higher in the trileaflet aortic valve compared to the bicuspid valve (4.0 +/- 0.1 versus 3.6 +/- 0.1 pM; p = 0.04).. Circulating plasma levels of ET-1 and BNP were decreased after surgery for aortic valve disease. The decrease was unrelated to the presence of ascending aortic aneurysm, and most likely represents a response to cardiac remodeling and the improved functional status of the patients.

Topics: Adult; Aged; Aged, 80 and over; Aortic Aneurysm; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Blood Vessel Prosthesis Implantation; Down-Regulation; Endothelin-1; Female; Heart Valve Prosthesis Implantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Recovery of Function; Stroke Volume; Sweden; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling