Integrin-linked kinase expression is elevated in human cardiac hypertrophy and induces hypertrophy in transgenic mice.
Lu H, Fedak PW, Dai X, Du C, Zhou YQ, Henkelman M, Mongroo PS, Lau A, Yamabi H, Hinek A, Husain M, Hannigan G, Coles JG.
Cancer Research Program, Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada..
Circulation. 2006 Nov 21;114(21):2271-9. Epub 2006 Nov 6.

• > BACKGROUND: Although numerous signaling pathways are known to be activated in experimental cardiac hypertrophy, the molecular basis of the hypertrophic response inherent in human heart diseases remains largely unknown. Integrin-linked kinase (ILK) is a multifunctional protein kinase that physically links beta-integrins with the actin cytoskeleton, suggesting a potential mechanoreceptor role.
  METHODS AND RESULTS: Here, we show a marked increase in ILK protein levels in hypertrophic ventricles of patients with congenital and acquired outflow tract obstruction. This increase in ILK was associated with activation of the Rho family guanine triphosphatases, Rac1 and Cdc42, and known hypertrophic signaling kinases, including extracellular signal-related kinases (ERK1/2) and p70 S6 kinase. Transgenic mice with cardiac-specific expression of a constitutively active ILK (ILK(S343D)) or wild-type ILK (ILK(WT)) exhibited a compensated ventricular hypertrophic phenotype and displayed an activation profile of guanine triphosphatases and downstream protein kinases concordant with that seen in human hypertrophy. In contrast, transgenic mice with cardiomyocyte-restricted expression of a kinase-inactive ILK (ILK(R211A)) were unable to mount a compensatory hypertrophic response to angiotensin II in vivo.
  CONCLUSIONS: Taken together, these results identify ILK-regulated signaling as a broadly adaptive hypertrophic response mechanism relevant to a wide range of clinical heart disease.

  NOTE: Please note that imaging in this paper was performed using our 1st generation instrument, the VS40. VisualSonics’ current generation instrument, the Vevo 770, has significantly improved performance in terms of functionality, frame rate, and overall utility.