Solution of the stochastic Langevin equations for clustering of particles in random flows in terms of the Wiener path integral.

We propose to take advantage of using the Wiener path integrals as the formal solution for the joint probability densities of coupled Langevin equations describing particles suspended in a fluid under the effect of viscous and random forces. Our obtained formal solution, giving the expression for the Lyapunov exponent, (i) will provide the description of all the features and the behavior of such a system, e.g., the aggregation phenomenon recently studied in the literature using appropriate approximations, (ii) can be used to determine the occurrence and the nature of the aggregation-nonaggregation phase transition which we have shown for the one-dimensional case, and (iii) allows the use of a variety of approximative methods appropriate for the physical conditions of the problem such as instanton solutions in the WKB approximation in the aggregation phase for the one-dimensional case as presented in this paper. The use of instanton approximation gives the same result for the Lyapunov exponent in the aggregation phase, previously obtained by other authors using a different approximative method. The case of nonaggregation is also considered in a certain approximation using the general path integral expression for the one-dimensional case.

Long-chain fatty acids modify hypertrophic responses of cultured primary neonatal cardiomyocytes.

In vivo, the normal heart obtains at least 60% of its energy from lipids and the remainder from glucose. Several lines of evidence indicate that an increase in the utilization of glucose [at the expense of fatty acids (FA)] may play a role in the genesis of hypertrophy. Primary cultures of neonatal cardiomyocytes have been used extensively to study the phenotype of these cells as well as their responses to hormonal hypertrophic agents. Unfortunately, such cultures are most typically cultured in glucose-rich FA-free media, and thus might be hypertrophied to start with. We therefore tested the effects of FA-albumin complexes on three different surrogate end points of hypertrophy of cardiomyocytes. Oleate-albumin complexes decreased the baseline values of all three variables, and increased the relative response of these variables to administration of norepinephrine. Oleate:palmitate-albumin complexes also affected all three variables and their responses to norepinephrine, but the effects differed somewhat from that of oleate-albumin complexes. Our results suggest that addition of long-chain FA, by providing conditions that more closely resemble physiological situations, may optimize the expression of hypertrophic responses in such cells. However, the differences between the effects of oleate and oleate:palmitate also suggest that the precise composition of FA may affect the phenotype of cardiomyocytes and how these cells respond to hypertrophic agents.

Functional alterations of the Nppa promoter are linked to cardiac ventricular hypertrophy in WKY/WKHA rat crosses.

Cardiac left ventricular hypertrophy (LVH) is commonly associated with hypertension, but its variance is determined for more than 50% by blood pressure-independent genetic factors. Because it constitutes one of the most important risk factors for cardiovascular mortality, we have performed a genome-wide scan of the F2 progeny of crosses between inbred WKY and WKHA rats to detect quantitative trait loci (QTL) linked to cardiac mass. In addition to left ventricular mass (LVM), we also measured left ventricle (LV) concentration of atrial natriuretic factor (ANF), because we have previously established that there was a genetic link between these 2 traits in the same animal cross. We found 2 contiguous QTL on chromosome 5 that were linked to either LVM (logarithm of odds [LOD]=3.5) or log(n) (LV ANF) (LOD=12). The 1-LOD support intervals of both QTL shared a region overlapping the locus of natriuretic peptide precursor A (NPPA:) (ie, the ANF-coding gene). We found by sequencing 2 single nucleotide polymorphisms (SNPs) within the first 650 bp of the NPPA: minimal promoters of the genes from both strains. One of these SNPs increased the transcriptional activity of the NPPA: minimal promoter in transfected neonatal cardiomyocytes in keeping with the higher LV concentration of ANF observed in WKY versus WKHA rats. Taken together with the previous reports showing that ANF may protect cardiomyocytes against hypertrophy, our genetic data single out NPPA: as a strong candidate gene for the determination of LVM.