Tissue inhibitor of metalloproteinase-1 (TIMP-1) as an independent marker of ischemic myocardial remodeling in heart failure

It has been reported that the increased expression of natural inhibitors of the matrix metalloproteinases is associated with the high risk of mortality and heart failure progression. The aim of the study was to estimate the diagnostic value of tissue inhibitor of metalloproteinase-1 (TIMP-1) for the diagnosis of heart failure in patients with myocardial ischemia and/or post-myocardial infarction remodeling. A total of 52 patients with heart failure NYHA classes II, III, and IV were enrolled in the study. Diagnostic value and prognosis for adverse cardiovascular events were analyzed in the prospective 6-month observation. The patients were divided into three groups according to heart failure severity: group 1 included patients with NYHA class II (n=18) with preserved left ventricular (LV) ejection fraction (EF) (>45%), group 2 included patients with NYHA class III (n=23) with decreased LV EF, and group 3 included patients with the most severe NYHA class IV chronic heart failure (n=11) and LV EF of <32.5%. The age of the patients was 60.6+0.92 years. The TIMP-1 level in blood was determined by hard phase immunoenzyme analysis. All-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), need for revascularization, need for hospitalization, and definite progression of heart failure were the clinical endpoints with 6-month follow-up. The TIMP-1 level in patients of group 1 ranged from 181 to 375.9 ng/ml (Me=278.45 ng/ml); patients in group 2 had TIMP-1 levels ranging from 376.6 to 897.8 ng/ml (Me=637.2 ng/ml), and the levels of TIMP in patients of group 3 were significantly higher, ranging from 903.6 to 1687.9 ng/ml (Me=1295.8 ng/ml). Two patients with end-stage heart failure from group 2 and group 3 died during the study; their TIMP-1 levels were 1289.9 and 1687 ng/ml, respectively. In patients with ischemic heart disease, heart failure, and postmyocardial infarction remodeling, TIMP-1 can be considered a new independent predictor of ischemic myocardial dysfunction and LV fibrosis.

биомаркер баланса коллагена, ингибитор матриксных протеиназ-1, ишемическое ремоделирование миокарда, сердечная недостаточность, диагностика, biomarkers of collagen metabolism, tissue inhibitors of matrix metalloproteinases, postmyocardial infarction remodeling, heart failure, diagnostics

1. Бушмакина А.В., Козиолова Н.А., Ковалевская Н.А. и др. Новый способ диагностики раннего субклинического поражения почек у больных гипертонической болезнью и возможности его коррекции в зависимости от тактики и выбора антигипертензивной терапии // Артериальная гипертензия. - 2012. - Т. 18, № 1. - С. 37-44.

2. Егорова Е.Н., Мазур В.В., Калинкин М.Н., Мазур Е.С. Взаимосвязь эндотоксемии, факторов системного воспаления и компонентов системы матриксных металлопротеиназ -тканевых ингибиторов металлопротеиназ при ХСН // Сердечная недостаточность. - 2012. - Т. 72, № 4. - С. 233-236.

3. Национальные рекомендации ВНОК и ОССН по диагностике и лечению ХСН (третий пересмотр, 2010). - М., 2010. - 112 с.

4. Свирида О.Н., Овчинников А.Г., Агеев Ф.Т. Влияние кандесартана и его комбинации со спиронолактоном на диастолическую функцию левого желудочка и содержание биохимических маркеров баланса коллагена у пациентов с ХСН и сохраненной систолической функцией левого желудочка // Сердечная недостаточность. - 2010. - Т. 61, № 5. - С. 263-275.

5. Рябов В.В., Шурупов В.С., Суслова Т.Е., Марков В.А. Характеристика ригидности магистральных артерий у больных хронической сердечной недостаточностью при сохраненной систолической функции сердца после инфаркта миокарда // Сибирский медицинский журнал (Томск). - 2011. - № 4, вып. 1. - С. 46-51.

6. Соломахина Н.И., Беленков Ю.Н. Прогностическое значение тканевого ингибитора матриксных металлопротеиназ-(TIMP-1) у больных ХСН // Сердечная недостаточность. - 2010. - Т. 61, № 5. - С. 281-284.

7. Тепляков А.Т. Хроническая сердечная недостаточность. Цитокиновая экспрессия, иммунная активация и защита органов-мишеней. - Томск: Изд-во Том. ун-та, 2012. -294 с.

8. Blankenberg S., Rupprecht H.J., Poirier O. et al. Plasma concentrations and genetic variation of matrix metalloproteinase-9 and prognosis of patients with cardiovascular disease // Circulation. - 2003. - Vol. 107(12). -P. 1579-1585.

9. Castro M.M., Rizzi E., Prado C.M. et al. Imbalance between matrix metalloproteinase and tissue inhibitor of metalloproteinases in hypertensive vascular remodeling // Matrix Biol. - 2010. -Vol. 29(3). - P. 194-201.

10. Cavusoglu E., Ruwende C., Chopra V. et al. Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac and myocardial infarction // Am. Heart J. - 2006. - Vol. 151(5). - P. 1101e1101-1101e1108.

11. Kelly D., Sguire J.B., Khan S.Q. et al. Usefulness of plasma tissue inhibitor of metalloproteinases as markers of prognosis after acute myocardial infarction // Am. J. Cardiol. - 2010. - Vol. 106(4). - P. 477-482.

12. Lim C.S., Shalhaub J., Gohel M.S. et al. Matrix metalloproteinase in vascular disease - a potential therapeutic target? // Cur. Vasc. Pharmacol. - 2010. - Vol. 8(1). - P. 75-85.

13. Lubos E., Schnabel R., Rupprecht H.J. et al. Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the atherogene study // Eur. Heart J. - 2006. - Vol. 27(2). - P. 150156.

14. Tayebjee M.H., Nadar S., Blann A.D. et al. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) // Am. J. Hypertens. - 2004. -Vol. 17(9). - P. 764-769.