lv surgical specimens were acquired from the lvot in adult patients n 4 with hypertrophic obstructive cardiomyopathy hocm exhibiting resting lvot gradients gt 50 mmhg control ventricular tissue was obtained from structurally normal hearts n 5 at the time of multi organ transplantation procurement myocardial samples from hocm patients exhibited a u02dc 2 fold increase in ilk protein levels relative to control hearts fig1 b thus the cases of clinical hypertrophy all demonstrate elevation of ilk protein suggesting this is a critical molecular response to increased cardiac loading and the development of hypertrophy ilk has been shown to activate rho family gtpases which have also been causally implicated in experimental hypertrophy we therefore assayed the ventricular tissues directly for activation of rhoa cdc42 and rac1 gtpases using specific affinity binding assays that distinguish the gdp bound inactive and gtp bound active states of each strikingly there was a u02dc 2 fold and 10 fold increase in rac1 gtp loading in the hypertrophic ventricular samples from patients with acquired and congenital and outflow tract obstruction respectively fig2 ab cdc42 activation of u02dc 2 fold was also evident in both acquired and congenital hypertrophic lesions conversely the levels of gtp bound rhoa were unchanged between the control and.