Epigallocatechin gallate for medical management of the abdominal aortic aneurysm

Abstract

Setozake et al1Setozaki S. Minakata K. Masumoto H. Hirao S. Yamazaki K. Kuwahara K. et al.Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model.J Vasc Surg. 2017; 65: 1803-18012.e2Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar reported in the Journal that the administration of epigallocatechin gallate (EGCG), extracted from green tea, prevents the progression of abdominal aortic aneurysms in a rat model.1Setozaki S. Minakata K. Masumoto H. Hirao S. Yamazaki K. Kuwahara K. et al.Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model.J Vasc Surg. 2017; 65: 1803-18012.e2Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar We are pleased to see this confirmation of the experiments we reported in 2004 to 2007. The roles for inflammation and autoimmunity in AAAs were proposed by Beckman,2Beckman E.N. Plasma cell infiltrates in atherosclerotic abdominal aortic aneurysms.Am J Clin Pathol. 1986; 85: 21-24Crossref PubMed Scopus (55) Google Scholar Koch et al,3Koch A.E. Haines G.K. Rizzo R.J. Radosevich J.A. Pope R.M. Robinson P.G. et al.Human abdominal aortic aneurysms: immunophenotypic analysis suggesting an immune-mediated response.Am J Pathol. 1990; 137: 1199-1213PubMed Google Scholar Brophy et al,4Brophy C.M. Reilly J.M. Smith G.J. Tilson M.D. The role of inflammation in nonspecific abdominal aortic aneurysm disease.Ann Vasc Surg. 1991; 5: 229-233Abstract Full Text PDF PubMed Scopus (210) Google Scholar and Tilson et al.5Gregory A.K. Yin N.X. Capella J. Xia S. Newman K.M. Tilson M.D. Features of autoimmunity in the abdominal aortic aneurysm.Arch Surg. 1996; 131: 85-88Crossref PubMed Scopus (119) Google Scholar It was known in the early 1990s that matrix metalloproteinases (MMPs) are important mediators of aortic destruction in AAAs.6Newman K.M. Jean-Claude J. Li H. Scholes J.V. Ogata Y. Nagase H. et al.Cellular localization of matrix metalloproteinases in the abdominal aortic aneurysm wall.J Vasc Surg. 1994; 20: 814-820Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar The sub-antimicrobial doxycycline was known to be an MMP inhibitor, and it had been approved for clinical use in periodontal disease. Accordingly, there was a strong rational for proposing doxycycline for clinical trial as a medical therapy for AAA. EGCG had also been found to be an inhibitor of MMP-2 derived from neoplastic cells. We found that EGCG reduced the activity of MMP-2 from cultured AAA fibroblasts in vitro by 50% at a dose of 1.25 μg/μL.7Toset A. Toumpoulis I. Collin P. Giangola G. Todd G. Tilson M.D. A comparison of two commercial inhibitors of aneurysm MMP-2 activity in vitro.J Surg Res. 2004; 121: 323Abstract Full Text PDF Google Scholar Further in vivo studies showed that EGCG reduced aortic dilation in the calcium chloride8Ro C.Y. Fukumoto R. DeRose J.J. Ryan S.W. Sagalovich D. Collin P. et al.AneuMastat(R) prevents aneurysm formation in a murine model of abdominal aortic aneurysm (AAA).J Am Coll Surg. 2006; 203: S103Abstract Full Text Full Text PDF Google Scholar and angiotensin II-induced9Tyrie L.S. Fujikura K. Luo J. Selegean S. Attiyeh M. Collin P. et al.AneuMastat reduces aneurysm incidence in the angiotensin II (AngII)-induced model of abdominal aortic aneurysm (AAA) in the wildtype C57BL6 mouse.J Am Coll Surg. 2007; 205: S111Abstract Full Text Full Text PDF Google Scholar mouse models. Thirteen randomized clinical trials have reported on drug therapies for AAAs in human subjects.10Golledge J. Moxon J.V. Singh T.P. Bown M.J. Mani K. Wanhainen A. Lack of an effective drug therapy for abdominal aortic aneurysm.J Intern Med. 2020; 288: 6-22Crossref PubMed Scopus (53) Google Scholar However, none of the therapies has been effective. More effort is clearly indicated. Pharmaceutical companies have had little interest in commercializing available natural products. Nutraceutical agents are stocked in drug stores with vitamins. It would take an eleemosynary entity to organize a proper clinical trial. Thus, we may never know whether EGCG is effective. ReplyJournal of Vascular SurgeryVol. 73Issue 4PreviewWe are pleased to read a letter from one of the expert researchers in the field, which once again demonstrated the validity of our experimental study.1 Full-Text PDF