Generation of Intracellular Signals by Low Density Lipoprotein Is Independent of the Classical LDL Receptor

Low density lipoprotein cholesterol (LDL) and apolipoprotein B-100 (1 to 15 μg/mL) had no significant influence on the inositol-1,4,5-trisphosphate (InsPa) formation in vascular smooth muscle cells and fibroblasts. Low density lipoprotein cholesterol (15 μg/mL) induced an elevation of intracellular Ca2+ from 85 to approximately 210 nmol/L in vascular smooth muscle cells from rat aorta in the absence or in the presence of 15 μg/mL monoclonal antibodies against the classical low density lipoprotein receptor or in the presence of apolipoprotein B-100. Moreover, in both human cultured fibroblasts from normocholesterolemic individuals and from patients with familial hypercholesterolemia homozygote class 1, LDL induced a dose-dependent rise of free intracellular calcium and a biphasic change of intracellular pH. Since homozygote class 1 fibroblasts are classical LDL receptor negative, and as antibodies against this receptor, as well as apolipoprotein B-100, did not attenuate the LDL-induced elevation of cytosolic calcium, we conclude that LDL might modify vascular activity via the observed intracellular changes without involving the classical low density lipoprotein receptor. Am J Hypertens 1991;4:274-27

Is there a Role for the ob Gene Product Leptin in Essential Hypertension?

In this study we wanted to evaluate the relationship between the ob gene product leptin and blood pressure, as well as plasma renin activity and plasma aldosterone levels. We studied 139 subjects with a mean ± SD age of 50 ± 14 years and a body mass index of 26.5 ± 5.3 kg/m2; 110 subjects had essential hypertension and 29 were healthy nonhypertensive controls. Blood pressure was measured in resting conditions in the morning and blood was drawn for the determination of the plasma renin activity, aldosterone, and leptin levels. The mean blood pressure of the population was 155/97 mm Hg. The relationship between these parameters was studied by univariate regression analysis according to gender and, whenever indicated, adjusted for age and body mass. The mean ± SEM plasma leptin level in the whole population was 9.5 ± 0.6 ng/mL (range, 1.1-43.3). Subjects with stage I hypertension had significantly higher plasma leptin levels than normotensive subjects. Systolic blood pressure correlated with the plasma leptin levels and the leptin levels adjusted for body weight in women (r = 0.422, P < .01) and nonhypertensive men (r = 0.644, P = .03) only. Plasma renin activity (r = 0.329, P = .03) and aldosterone levels (r = 0.342, P = .026) correlated with the leptin concentration. A significant relationship between the peripheral expression of the ob gene product leptin and systolic blood pressure was found in women and nonhypertensive men. In view of the multiple functions of leptin a causal relationship is postulated and potential mechanisms may involve modulatory effects of leptin on neuropeptide Y, angiotensinogen gene expression, the modulation of the autonomous nervous system, or effects on the pituitary adrenal axis. Direct relationships between both plasma renin activity and aldosterone levels and leptin support the potential importance of the relationship between leptin and blood pressure. Our observation may be of future importance for the understanding of the link between the increase in blood pressure and increasing body weigh

The functions of narrative passages in three written online health contexts

This paper investigates and compares the functions of narrative passages in three computer-mediated health practices centering on advice-giving: (1) email counseling at a UK university, (2) online forums providing peer support for smoking quitters, and (3) anti-smoking websites by UK governmental, commercial and charitable institutions. We found that the functions of the narrative passages are manifold and often overlapping. They range from seeking advice, giving advice, indicating/seeking agreement, supporting a claim, showing compliance with advice given to reporting on progress and success. In a second step, these insights were linked to how the narrative passages were used for identity construction and relational work. The results show that narratives are employed to create various identities, such as authentic advice-seekers, active self-helpers, successful quitters and advice-givers. Our comparison reveals that narrative functions utilized in all three practices exhibit nuanced differences due to medium factors and interactional goals of the practices. Finally, in these contexts of self-improvement, narratives document stability or transformation in the sense of clients’ improved health and smokers’ change to becoming non-smokers respectively

P-2: Human vascular smooth muscle cell DNA synthesis stimulated by native low density lipoproteins involves redox-sensitive pathways. Inhibition by N-acetylcysteine and green tea constituents

High plasma concentrations of LDL are an important cardiovascular risk factor. The mechanisms involved in DNA synthesis induced by native LDL in human vascular smooth muscle cells are unclear. We investigated the potential role of oxidative stress in human vascular smooth muscle cells (VSMC) DNA synthesis using the antioxidant N-acetylcysteine (NAC) and different green tea catechins, i. e. epigallocatechin (EGC), epigallocatechin gallate (EGCg) and green tea polyphenon, a mixture of green tea catechins at physiological concentrations (0.01-1 g/mL). DNA synthesis was determined using radiolabeled thymidine incorporation, oxidative susceptibility of human serum was studied using 2,2'-azobis(2-amidinopropane) (AAPH). Data are expressed as percent of control. LDL (100 μg/mL LDL protein) increased DNA synthesis by 165% (from 100±3 to 265±6%, p<0.05), an effect that was completely blocked by pretreatment with the antioxidant N-acetylcysteine (98±22%, p<0.0001 vs. LDL). Similarly, epigallocatechin and epigallocatechin gallate concentration-dependently inhibited LDL-induced DNA synthesis to 122±4% and 117±4%, respectively (P<0.001 vs. LDL). Coincubation of both EGC and EGCg completely prevented LDL-induced DNA synthesis (92±2%, p<0.001 vs. LDL). Polyphenon alone reduced to DNA synthesis to 170±6%(p<0.05 vs. LDL), being less potent than the combination of EGC+EGCg, and also inhibited serum oxidation by 46±8% (p<0.05). However, combination of NAC and polyphenon markedly inhibited LDL synthesis below control levels (21±9%, p<0.0001 vs. LDL and control). Treatments had no effect on cell viability as determined by LDH release and Tryphan blue tests. These results demonstrate for the first time that LDL-induced DNA synthesis in human vascular smooth muscle cells involves redox-sensitive pathways that can be inhibited by physiological concentrations of green tea catechins and/or non-specific antioxidants. Antioxidant therapy may therefore be beneficial in inhibiting the growth-promoting effects of native LDL in human vascular smooth muscle cell

Linguistic expert creation in online health practices

In this chapter, we explore how the construction of an expert identity varies across online e-health settings with different socio-technological features. Our methodology is qualitative in nature and draws on insights from discourse analysis, in particular positioning theory. Results show that four aspects of creating expertise are vital: the embeddedness of the posi-tioning strategies in the online health context, the interplay between these strategies within each setting, the interactivity of the medium, and the fact that not only professionals, but also clients and laypeople construct their expertise. The results reveal that previously found strategies to create expertise (e.g., using jargon or showing empathy) could be confirmed in our corpus, and that the interplay of several strategies is in fact needed to create credible and trustworthy expert identities for all participants involved. This interplay varies accord-ing to the practice

Generation of Intracellular Signals by Low Density Lipoprotein Is Independent of the Classical LDL Receptor

Low density lipoprotein cholesterol (LDL) and apolipoprotein B-100 (1 to 15 μg/mL) had no significant influence on the inositol-1,4,5-trisphosphate (InsPa) formation in vascular smooth muscle cells and fibroblasts. Low density lipoprotein cholesterol (15 μg/mL) induced an elevation of intracellular Ca2+ from 85 to approximately 210 nmol/L in vascular smooth muscle cells from rat aorta in the absence or in the presence of 15 μg/mL monoclonal antibodies against the classical low density lipoprotein receptor or in the presence of apolipoprotein B-100. Moreover, in both human cultured fibroblasts from normocholesterolemic individuals and from patients with familial hypercholesterolemia homozygote class 1, LDL induced a dose-dependent rise of free intracellular calcium and a biphasic change of intracellular pH. Since homozygote class 1 fibroblasts are classical LDL receptor negative, and as antibodies against this receptor, as well as apolipoprotein B-100, did not attenuate the LDL-induced elevation of cytosolic calcium, we conclude that LDL might modify vascular activity via the observed intracellular changes without involving the classical low density lipoprotein receptor. Am J Hypertens 1991;4:274-27

The platelet-derived growth factor isomers, PDGF-AA, PDGF-AB and PDGF-BB, induce contraction of vascular smooth muscle cells by different intracellular mechanisms

AbstractThe effect of human recombinant platelet-derived growth factor (PDGF) isoforms, (r)PDGF-AA, PDGF-AB and PDGF-BB, on contractility of rat aortic rings as well as on intercellular free Ca2+ ([Ca2+]i), intracellular pHi (pHi) and thromboxane A2 (TXA2) formation in cultured vascular smooth muscle cells (VSMC) was examined. PDGF-BB behaved similar to PDGF-AB and both have features characteristic of conventional vasocontrictor-agonists that directly increase [Ca2+]i, activate the Na+/H+ exchanger, stimulate the TXA2 formation, and induced contraction in VSMC whereas PDGF-AA induced contraction without increasing of [Ca2+]i, pHi, and TXA2 formation