BASIC RESEARCH

Deficiency of ß1 integrins results in increased myocardial dysfunction after myocardial infarction

P Krishnamurthy, V Subramanian, M Singh, K Singh

Department of Physiology, James H Quillen College of Medicine, James H Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, Tennessee, USA

Correspondence to:
Professor Krishna Singh
Department of Physiology, James H Quillen College of Medicine, East Tennessee State University, PO Box 70576, Johnson City, TN 37614, USA; singhk{at}etsu.edu

Objective: To study the role of ß1 integrins in left ventricular (LV) remodelling after myocardial infarction (MI).

Methods and results: LV structural and functional alterations were determined in wild-type (WT) and ß1 integrin heterozygous knockout (hKO) mice one month after MI. MI increased ß1 integrin expression in both groups; however, the increase was lower in hKO. Infarct size was similar in WT and hKO mice, whereas lung wet weight to dry weight ratio was increased in the hKO-MI mice (5.17 (SE 0.13) v 4.60 (0.15) in WT-MI, p < 0.01). LV end systolic and end diastolic diameters were significantly higher and percentage fractional shortening was significantly lower in hKO-MI. The ratio of peak velocity of early LV filling (E wave) to that of the late LV filling (A wave) and the isovolumic relaxation time (IVRT) were increased in both MI groups but the increase in IVRT was significantly higher in hKO-MI group than in WT-MI mice. Langendorff perfusion analysis indicated reduced peak LV developed pressure and increased LV end diastolic pressure in both MI groups. The reduction in peak LV developed pressure (36.7 (2.2) v 53.4 (1.9) mm Hg, p < 0.05) and increase in LV end diastolic pressure was higher in hKO-MI than in WT-MI. Increase in fibrosis was not different between the two MI groups. The increase in myocyte circumference was higher in the hKO-MI group (p < 0.001 v WT-MI). The number of apoptotic myocytes was significantly higher in hKO-MI than in WT-MI mice (p < 0.005) three days after MI. The number of necrotic myocytes was not different between the two MI groups.

Conclusion: ß1 integrins are crucial in post-MI remodelling with effects on LV function, hypertrophy and apoptosis.

Abbreviations: %FS, percentage fractional shortening; hKO, heterozygous knockout; ISOL, in situ oligo ligation; IVRT, isovolumic relaxation time; KH, Krebs–Henseleit; LV, left ventricular; LVEDD, left ventricular end diastolic diameter; LVESD, left ventricular end systolic diameter; MI, myocardial infarction; Tacß_1A, Tac subunit of the interleukin 2 receptor fused to the cytoplasmic domain of ß1A integrin; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling; WT, wild type

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