Atherosclerosis 179 (2005) 353–359 Temporal association between circulating proteolytic, inflammatory and neurohormonal markers in patients with coronary ectasia Ariel Finkelstein 1 , Yoav Michowitz 1 , Anastasia Abashidze, Hylton Miller, Gad Keren, Jacob George ∗ The Department of Cardiology, Tel Aviv Sourasky Medical Center, 6 Weizmann St. Tel Aviv, Israel Received 3 June 2004; received in revised form 9 August 2004; accepted 1 October 2004 Available online 22 December 2004 Abstract Background: The prevalence of coronary ectasia (CE) appears to rise in recent years. However, the pathogenetic mechanisms that underlie this entity are not understood. We hypothesized that dysregulation of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) contributes to ectasia formation. We also evaluated the association of MMP with inflammatory or the neurohormonal markers. Methods: We screened coronary angiographic procedures conducted in our hospital. Thirty-four patients with CEs were identified; 17 with a single ectasia and 17 with generalized ectasias. Two control groups; patients with atherosclerotic coronary disease (n = 26) and patients with normal coronary arteries (n = 27) were chosen randomly. Serum levels of MMP-2, MMP-3 and TIMP-1 were determined by ELISA. Pro B-type natriuretic peptide (proBNP) and high sensitivity C-reactive protein (hsCRP) serum levels were also measured. Results: Serum levels of MMP-2, MMP-3, TIMP-1, proBNP and hsCRP did not differ between the three groups of patients. However, subgroup analysis demonstrated that MMP-3 level is significantly lower in patients with generalized CEs compared to those with single vessel ectasia. We also found a statistically significant correlation between proBNP and MMP-2/TIMP-1 (for MMP-2: r 2 = 0.3, p = 0.003 and for TIMP-1 r 2 = 0.42, p < 0.000l). By performing subgroup analysis we found that this correlation is only demonstrated in patients with CEs. No correlation was demonstrated between hsCRP and MMPs/TIMP. Conclusions: These observations suggest that MMP/TIMP imbalance is present in patients with generalized CE and may contribute to ectasia formation. This imbalance could be mediated by BNP. © 2004 Published by Elsevier Ireland Ltd. Keywords: Coronary ectasia; Angiographic procedures; Serum levels 1. Introduction Coronary ectasia (CE) is an angiographic finding whose prevalence in different reports is in the range of 1.2–4.9% [1,2]. Clinically, it predisposes to adverse coronary events like vasospasm, thrombosis and dissection [1]. In recent years CE incidence is rising; however, whether this is related to higher incidence of angiographic and angioplastic procedures is not known [1]. Despite growing prevalence, controversy ∗ Corresponding author. Fax: +972 3 5469832. E-mail address: iacobg@post.tau.ac.il (J. George). 1 Authors equally contributed to the manuscript. still exists as to the pathogenetic mechanisms that underlie this entity. An increased incidence of CE has been reported in several disorders. Examples include atherosclerotic vascular disease [1,3], heterozygous familial hypercholesterolemia [4], usage of substances including herbicide spray, acetylcholinesterase inhibitors and nitrates (possibly through their action to stimu- lates no production) [5], previous arterial balloon angioplasty [6], polyarteritis nodosa [1] and Kawasaki syndrome [7]. Matrix metalloproteinases (MMPs) are a group of enzymes that degrade components of the extracellular matrix. These proteinases play a central role in many biological pro- cesses, such as embryogenesis, wound healing, angiogenesis, 0021-9150/$ – see front matter © 2004 Published by Elsevier Ireland Ltd. doi:10.1016/j.atherosclerosis.2004.10.020