Fetal Exposure to Maternal Low Protein Diet Programmes Cardiovascular Disease: Cardiac Phosphoinositide-Phospholipase C Isoenzymes in Hypertensive Weaning Pups
P.S. Tappia, V. Panagia, N. Sahi, R. Sherman1, S.C. Langley-Evans2 and A.A. Jackson1.
Institute of Cardiovascular Sciences, University of Manitoba, Canada, 1Institute of Human Nutrition, University of Southampton, U.K, 2Division of Life Sciences, Nene University College, U.K.
Several epidemiological studies in human populations in Europe, North America and the developing countries have demonstrated a link between low birth weight and poor early growth, and increased prevalence of non communicable diseases such as hypertension, stroke, type 2 diabetes and coronary heart disease in later life. It has been proposed that predisposition to these diseases may arise as a consequence of 'in utero genetic imprinting', when a stimulus or insult during gestation leads to irreversible adaptations in the structure and function of target organs. Our studies in rats showed that normally nourished weaning pups (3-4 weeks of age) which had been exposed to maternal low protein diet during fetal life and experienced disproportionate early growth, display significantly elevated systolic blood pressure (15-30 mmHg above controls) with attendant increased afterload to the heart and cardiac hypertrophy. Phosphoinositide-phospholipase C (PLC) isoenzymes are involved in several transmembrane signals which influence cardiac function. Angiotensin II, which is considered a factor in intrauterine programmed hypertension as well as in triggering pathological hypertrophy, acts through the PLC class. Thus, we examined the expression and activity of PLC 1 and, comparatively, of PLC ë1, another major PLC isoenzyme, in hearts of 4 wk old normally nourished male offspring whose mothers were fed on semi-purified diets containing either 180 (normal) or 90 g (low) casein/kg diet for 2 wks before mating and throughout pregnancy. Sarcolemmal (SL) PLC 1 activity and immunoprotein expression were depressed in  low  protein exposed offspring. In contrast, a 2-fold elevation in SL PLC ë1 activity with a concomitant increase in protein abundance was observed in this group. The results suggest that differential changes in PLC isoenzymes may, in part, contribute to the development of cardiac dysfunction secondary to hypertension. However, intrauterine programming of primary myocardial disease cannot be excluded. [Supported by MRC, Canada (VP) and MRC, U.K. (RS)].