Article Text

PDF
Deficiency of β1 integrins results in increased myocardial dysfunction after myocardial infarction
  1. P Krishnamurthy,
  2. V Subramanian,
  3. M Singh,
  4. K Singh
  1. Department of Physiology, James H Quillen College of Medicine, James H Quillen Veterans Affairs Medical Center, East Tennessee State University, Johnson City, Tennessee, USA
  1. 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

Abstract

Objective: To study the role of β1 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 β1 integrin heterozygous knockout (hKO) mice one month after MI. MI increased β1 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: β1 integrins are crucial in post-MI remodelling with effects on LV function, hypertrophy and apoptosis.

  • %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
  • Tacβ1A, Tac subunit of the interleukin 2 receptor fused to the cytoplasmic domain of β1A integrin
  • TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling
  • WT, wild type

Statistics from Altmetric.com

Footnotes

  • Published Online First 17 March 2006

  • This work is supported by National Institutes of Health, Grant number HL-071519 (KS), a Merit Review Grant from the Department of Veterans Affairs (KS) and a postdoctoral fellowship from the American Heart Association, Southeast Affiliate (PK).

  • Competing interests: None declared

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.