Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins. Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic. ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis. The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months. These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months. The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process.

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Nitric oxide produced in endothelial cells affects vascular tone. To investigate the role of endothelial nitric oxide synthase (eNOS) in blood pressure regulation, we have generated mice heterozygous (؉͞؊) or homozygous (؊͞؊) for disruption of the eNOS gene. Immunohistochemical staining with anti-eNOS antibodies showed reduced amounts of eNOS protein in ؉͞؊ mice and absence of eNOS protein in ؊͞؊ mutant mice. Male or female mice of all three eNOS genotypes were indistinguishable in general appearance and histology, except that ؊͞؊ mice had lower body weights than ؉͞؉ or ؉͞؊ mice. Blood pressures tended to be increased (by approximately 4 mmHg) in ؉͞؊ mice compared with ؉͞؉, while ؊͞؊ mice had a significant increase in pressure compared with ؉͞؉ mice (Ϸ18 mmHg) or ؉͞؊ mice (Ϸ14 mmHg). Plasma renin concentration in the ؊͞؊ mice was nearly twice that of ؉͞؉ mice, although kidney renin mRNA was modestly decreased in the ؊͞؊ mice. Heart rates in the ؊͞؊ mice were significantly lower than in ؉͞؊ or ؉͞؉ mice. Appropriate genetic controls show that these phenotypes in F 2 mice are due to the eNOS mutation and are not due to sequences that might differ between the two parental strains (129 and C57BL͞6J) and are linked either to the eNOS locus or to an unlinked chromosomal region containing the renin locus. Thus eNOS is essential for maintenance of normal blood pressures and heart rates. Comparisons between the current eNOS mutant mice and previously generated inducible nitric oxide synthase mutants showed that homozygous mutants for the latter differ in having unaltered blood pressures and heart rates; both are susceptible to lipopolysaccharide-induced death.

In recent years there has been an accumulation of evidence for the existence of nanobubbles on hydrophobic surfaces in water, despite predictions that such small bubbles should rapidly dissolve because of the high internal pressure associated with the interfacial curvature and the resulting increase in gas solubility. Nanobubbles are of interest among surface scientists because of their potential importance in the long-range hydrophobic attraction, microfluidics, and adsorption at hydrophobic surfaces. Here we employ recently developed techniques designed to induce nanobubbles, coupled with high-resolution tapping-mode atomic force microscopy (TM-AFM) to measure some of the physical properties of nanobubbles in a reliable and repeatable manner. We have reproduced the earlier findings reported by Hu and co-workers. We have also studied the effect of a wide range of solutes on the stability and morphology of these deliberately formed nanobubbles, including monovalent and multivalent salts, cationic, anionic, and nonionic surfactants, as well as solution pH. The measured physical properties of these nanobubbles are in broad agreement with those of macroscopic bubbles, with one notable exception: the contact angle. The nanobubble contact angle (measured through the denser aqueous phase) was found to be much larger than the macroscopic contact angle on the same substrate. The larger contact angle results in a larger radius of curvature and a commensurate decrease in the Laplace pressure. These findings provide further evidence that nanobubbles can be formed in water under some conditions. Once formed, these nanobubbles remain on hydrophobic surfaces for hours, and this apparent stability still remains a well-recognized mystery. The implications for sample preparation in surface science and in surface chemistry are discussed.