To assess the effects on the biosynthesis of collagen types I and III associated with an acute increase in blood pressure, we established a mid-thoracic aortic coarctation in the rabbit and studied gene expression and protein accumulation of these collagen types proximal to the stenosis 1, 3 and 7 days and 2, 4 and 8 weeks after coarctation. The mRNA level of type I collagen pro-α2(I) was maximal at 3 days and returned to normal at 4 weeks. mRNA of pro-α2(I) was localized mainly in the outer media, adventitia and intima. Accumulation of type I collagen and its precursors was increased by 3 days, peaked at 4 weeks, and decreased toward normal by 8 weeks, corresponding to the distribution of pro-α2(I) mRNA. Gene expression for pro-α1(III) was similar to that of pro-α2(I) but was distributed throughout the media. We conclude that the mechanical stresses associated with an acutely induced alteration in pressure initiate rapid gene expression for collagen types I and III in the aortic wall. The response for collagen type I, predominantly in the outer media and adventitia, suggests that these regions play an immediate role in the resistance to excessive dilatation of the aorta. The diffuse response for collagen type III in the media suggests participation in a more extensive remodeling response associated with the reinforcement and reorganization of the musculo-elastic fascicles.

Keywords:
Collagen, Extracellular matrix, Aortic coarctation, Hypertension
1.
Leung DYM, Glagov S, Mathews MB: Elastin and collagen accumulation in rabbit ascending aorta and pulmonary trunk during postnatal growth: Correlation of cellular synthetic response with medial tension. Circ Res 1977;41:316–323.
2.
Leung DYM, Glagov S, Mathews MB: Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. Science 1976;191:475–477.
3.
Clark JM, Glagov S: Structural integration of the arterial wall. I. Relationships and attachments of medial smooth muscle cells in normally distended and hyperdistended aortas. Lab Invest 1979;40:587–602.
4.
Wolinsky H, Glagov S: Structural basis for the static mechanical properties of the aortic media. Circ Res 1964;14:400–413.
5.
Clark JM, Glagov S: Transmural organization of the arterial media: The lamellar unit revisited. Arteriosclerosis 1985;5:19–34.
6.
Chapman D, Weber KT, Eghbali M: Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium. Circ Res 1990;67:787–794.
7.
Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ: Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 1979;18:5294–5299.
8.
Ausubel FM, Brent R, Kinston RE, Moore DD, Seidman JG, Smith JA, Struhl K (eds): Current Protocols in Molecular Biology. New York, John Wiley & Sons, vol 1 & 2, 1989.
9.
Glagov S, Grande J, Vesselinovitch D, Zarins CK: Quantitation of cells and fibers in histologic sections of arterial walls: Advantages of contour tracing on a digitizing plate; in McDonald TF, Chandler AB (eds): Connective Tissues in Arterial and Pulmonary Disease. New York, Springer, 1981, pp 57–93.
10.
Sage H, Bornstein P: Preparation and characterization of procollagens and procollagen-collagen intermediates. Methods Enzymol 1982;82:96–127.
11.
Butkowski RJ, Noelken ME, Hudson BG: Estimation of the size of collagenous protein by electrophoresis and gel chromatography. Methods Enzymol 1982;82:410–423.
12.
Miller EJ, Gay S: Collagen: An overview. Methods Enzymol 1982;82:3–33.
13.
Masawa N, Glagov S, Zarins CK: Quantitative morphologic study of intimal thickening at the human carotid bifurcation. I. Axial and circumferential distribution of maximum intimal thickening in asymptomatic, uncomplicated plaques. Atherosclerosis 1994;107:137–146.
14.
Masawa N, Glagov S, Zarins CK: Quantitative morphologic study of intimal thickening at the human carotid bifurcation. II. The compensatory enlargement response and the role of the intima in tensile support. Atherosclerosis 1994;107:147–155.
15.
Prosser IW, Stenmark KR, Suthar M, Crouch EC, Mecham RP, Parks WC: Regional heterogeneity of elastin and collagen gene expression in intralobar arteries in response to hypoxic pulmonary hypertension as demonstrated by in situ hybridization. Am J Pathol 1989;135:1073–1088.
16.
Sun R, Yan Y, Chen X, Si Q, Li H: Role of collagen metabolism changes in the pathogenesis of pulmonary hypertension in rats and its reversibility. Chin Med Sci J 1994;9:183–186.
17.
Bishop JE, Butt R, Dawes K, Laurent G: Mechanical load enhances the stimulatory effect of PDGF on pulmonary artery fibroblast procollagen synthesis. Chest 1998;114(1 suppl):25S.
18.
Durmowicz AG, Parks WC, Hyde DM, Mecham RP, Stenmark KR: Persistence, re-expression, and induction of pulmonary arterial fibronectin, tropoelastin, and type I procollagen mRNA expression in neonatal hypoxic pulmonary hypertension. Am J Pathol 1994;145:1411–1420.
19.
Zhang K, Gharaee-Kermani M, McGarry B, Phan SH: In situ hybridization analysis of rat lung alpha 1(I) and alpha 2(I) collagen gene expression in pulmonary fibrosis induced by endotracheal bleomycin injection. Lab Invest 1994;70:192–202.
20.
Shi Y, O’Brien JE Jr, Ala-Kokko L, Chung W, Mannion JD, Zalewski A: Origin of extracellular matrix synthesis during coronary repair. Circulation 1997;95:997–1006.
21.
Wilcox JN, Scott NA: Potential role of the adventitia in arteritis and atherosclerosis. Int J Cardiol 1996;54:S21–S35.
22.
Halloran BG, Baxter BT: Pathogenesis of aneurysms. Semin Vasc Surg 1995;8:85–92.
23.
Smith BD, McKenny KH, Lustberg TJ: Characterization of collagen precursors found in rat skin and rat bone. Biochemistry 1977;16:2980–2985.
24.
Yamamoto K, Yamamoto M: Cell adhesion receptors for native and denatured type I collagens and fibronectin in rabbit arterial smooth muscle cells in culture. Exp Cell Res 1994;214:258–263.
25.
Staatz WD, Walsh JJ, Pexton T, Santoro SA: The alpha 2 beta 1 integrin cell surface collagen receptor binds to the α1(I)-CB3 peptide of collagen. J Biol Chem 1990;265:4778–4781.
26.
Staatz WD, Fok KF, Zutter MM, Adams SP, Rodriguez BA, Santoro SA: Identification of a tetrapeptide recognition sequence for the α2β1 integrin in collagen. J Biol Chem 1991;266:7363–7367.
27.
Powell JT, Adamson J, MacSweeney ST, Greenhalgh RM, Humphries SE, Henney AM: Influence of type III collagen genotype on aortic diameter and disease. Br J Surg 1993;80:1246–1248.
28.
Xu ZL: Study of collagen abnormality in Marfan’s syndrome (in Chinese). Chung-Hua Ping Li Hsueh Tsa Chih 1992;21:164–166.
29.
Ferguson JC, Barrie WW, Schenk WG Jr: Hypertension of aortic coarctation: The role of renal and other factors. Ann Surg 1977;185:423–428.
30.
Zarins CK, Bomberger RA, Taylor KE, Glagov S: Artery stenosis inhibits regression of diet-induced atherosclerosis. Surgery 1980;88:86–92.
31.
Arnal JF, Battle T, Rasetti C, Challah M, Costerousse O, Vicaut E, Michel JB, Alhenc-Gelas F: Three tunicae of rat aorta: Expression in smooth muscle and effect of renovascular hypertension. Am J Physiol 1994;267:H1777–1784.
32.
Bishop JE, Lindahl G: Regulation of cardiovascular collagen synthesis by mechanical load. Cardiovasc Res 1999;42:27–44.
33.
Tozzi CA, Thakker-Varia S, Yu SY, Bannett RF, Peng BW, Poiani GJ, Wilson FJ, Riley DJ: Mast cell collagenase correlates with regression of pulmonary vascular remodeling in the rat. Am J Respir Cell Mol Biol 1998;18:497–510.
34.
Chobanian AV: Vascular effects of systemic hypertension. Am J Cardiol 1992;69:3E–7E.
35.
Bassiouny HS, Lieber BB, Giddens DP, Xu CP, Glagov S, Zarins CK: Quantitative inverse correlation of wall shear stress with experimental intimal thickening. Surg Forum 1988;39:328–330.
36.
Baron BW, Glagov S, Giddens DP, Zarins CK: Effect of coarctation on matrix content of experimental aortic atherosclerosis: Relation to location, plaque size and blood pressure. Atherosclerosis 1993;102:37–49.
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2000
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