Synthesis of tissue inhibitor of metalloproteinase-1 (TIMP-1) in rabbit aortic neointima after selective de-endothelialization

• Published in: Atherosclerosis Vol. 126; no. 1; pp. 95 - 104
• Main Authors: Wang, He, Moore, Sean, Alavi, Misbahuddin Zafar
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ireland Ltd 27.09.1996; Elsevier
• Subjects: Amino Acid Sequence; Animals; Aorta - metabolism; Atherosclerosis; Base Sequence; Biological and medical sciences; Catheterization - adverse effects; Diseases of the cardiovascular system; DNA, Complementary - genetics; Endothelium, Vascular - injuries; Extracellular matrix; Gene expression; Glycoproteins - biosynthesis; Glycoproteins - genetics; In situ hybridization; Injury; Male; Medical sciences; Molecular Sequence Data; Muscle, Smooth, Vascular - metabolism; Rabbits; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; RT-PCR; TIMP; Tissue Inhibitor of Metalloproteinases; Injury; RT-PCR; Atherosclerosis; Extracellular matrix; Gene expression; In situ hybridization; TIMP; Postoperative; Instrumentation therapy; Rabbit; Cardiovascular disease; Exploration; Instrumental dilatation; Lagomorpha; Vertebrata; Mammalia; Treatment; Animal; Aorta; Aortic disease
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/0021-9150(96)05898-4

Altered TIMP-1 synthesis in the arterial wall may be important for the balance between metalloproteinases and their inhibitors, and thus contribute to dysregulated extracellular matrix metabolism in atherosclerotic lesions. To examine this, we cloned the rabbit TIMP-1 gene from aortic neointima, developed in response to a balloon-catheter induced de-endothelialization. The apparent homology of cDNA with TIMP-1 genes from several sources suggested that it is a rabbit form of TIMP-1. We examined the recombinant rabbit TIMP-1 expression in Escherichia coli using the pTrxFus expression system and the synthesis of the resulting soluble protein was confirmed by immunostaining with anti-TIMP-1. The TIMP-1 concentration in normal and de-endothelialized rabbit aortas was compared using Northern blot, Western blot and mRNA in situ hybridization techniques. We observed a significant increase of TIMP-1 expression in neointimal SMCs at both nucleic acid and protein levels, suggesting a role of TIMP-1 in injury-induced atherogenesis.