Effect of low-density lipoprotein on intracellular calcium, intracellular pH and DNA synthesis in cultured vascular smooth muscle cells

Sachinidis, Agapios; Locher, Rudolf; Steiner, Albert; Mengden, Thomas; Vetter, W

doi:10.1097/00004872-198900076-00054

Cited by 11 publications

(6 citation statements)

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“…Similarly, parallel hyperaggregation and platelet release reactions have been observed in NIDDM patients with and without hypertension (205). The platelet has been described as a surrogate for vascular smooth muscle cells (VSMC) (381,437), and the observation that LDL cholesterol acutely increases [Ca2+Ii in VSMC (339,358) as well as platelets (20,24,25,161,162,219,375) supports the similarity of these cell types. In general, it has been observed that the platelet [Ca2+Ii response to agonists such as LDL (20,24,161,162,375) and thromboxane (87) is enhanced only in NIDDM patients who demonstrate exaggerated platelet aggregation.…”

Section: Picitelet Adhesion and Platelet Aggregationmentioning

confidence: 93%

“…Increased platelet membrane cholesterol to phospholipid content is, in turn, associated with increased platelet [Ca2+Ii responses to agonists (20,189,190,261). Another mechanism that appears to contribute to enhanced platelet [Ca2+Ii responses, aggregation, and release reactions (70,205,393) in patients with diabetes mellitus is the increased nonenzymatic glycosylation of platelet membrane proteins (340), which decreases membrane fluidity and enhances the [Ca2+],, aggregation, and release responses to agonists (205,243,269,309,339,358,436). Resistance to the normal actions of insulin as occurs in hypertension and NIDDM (1 17,308,368,370,372,374, 377) could also potentially contribute to enhanced [Ca2 'Ii increases and associated hyperaggregation (205,397) and release (205), as insulin has been observed to attenuate platelet [Ca2 'Ii and aggregation responses (123,412) (similar to effects seen in VSMC (174,202,278,3 14)).…”

Section: Picitelet Adhesion and Platelet Aggregationmentioning

confidence: 99%

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Diabetes Mellitus and Hypertension, Emerging Therapeutic Perspectives

Sowers

Epstein

1995

Cardiovascular Drug Reviews

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Section: Picitelet Adhesion and Platelet Aggregationmentioning

confidence: 93%

Section: Picitelet Adhesion and Platelet Aggregationmentioning

confidence: 99%

Diabetes Mellitus and Hypertension, Emerging Therapeutic Perspectives

Sowers

Epstein

1995

Cardiovascular Drug Reviews

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“…155,156 Low-density lipoproteins cause a dose-dependent [Ca 2ϩ ] i increase in cultured rat VSMC, mediated by substantially enhanced Ca 2ϩ influx and by mobilization of Ca 2ϩ stores. 157 It is important to mention that Ca 2ϩ influx in cultured rat VSMC is augmented not only by LDL but also by HDL 3 , the extent of cell signaling elicited by both lipoprotein fractions being almost identical. 158 This could explain a cosegregation of BP with these two lipoprotein fractions in Lyon F 2 hybrids.…”

Section: Cell Calcium Handlingmentioning

confidence: 97%

Abnormalities of membrane function and lipid metabolism in hypertension A review

Zicha

Kuneš

Devynck

1999

American Journal of Hypertension

212

175

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Hypertension, which is characterized by multiple alterations in the structure and function of the cell membrane, is often associated with important metabolic abnormalities including those concerning lipid metabolism. Dyslipidemia accompanying essential hypertension consists of elevated plasma triglycerides, low HDL cholesterol, and increased levels of atherogenic LDL cholesterol particles. The altered membrane microviscosity seen in hypertensive subjects reflects the changes of membrane lipid composition resulting from intensive exchange between circulating and membrane lipids, as well as from abnormal cellular lipid synthesis and metabolism. The changes of membrane microviscosity are known to modulate the activity of proteins involved in ion transport, signal transduction, cell Ca 2؉ handling, intracellular pH regulation, etc. Alterations in plasma or membrane lipids are indeed closely associated with ion transport abnormalities as well as with impaired control of cytosolic Ca 2؉ T here is no doubt that essential hypertension is associated with multiple membrane alterations, including changes in membrane microviscosity, receptor function, signal transduction, ion transport, calcium mobilization, intracellular pH regulation, and so on. Lipids, as an integral part of the cell membrane, play a decisive role in the modulation of the membrane properties mentioned. Specific lipid-lipid and lipid-protein interactions result in a highly dynamic but precisely controlled architecture of membrane components. Major regulators of membrane architecture are membrane potential, intracellular Ca 2ϩ and pH, lipid composition, cell-to-cell contact, and membrane coupling with the cytoskeleton or extracellular matrix. Intermolecular associations in the membrane and at the membrane-cytoskeleton interface are further selectively controlled by specific phosphorylation and dephosphorylation cascades involving both proteins and lipids. This is regulated by the extracellular matrix as well as by the binding of growth factors and hormones to their specific receptors. 1,2The aim of this review is to outline some interrelationships between abnormal lipid metabolism and altered membrane structure or function in human and experimental hypertension, and to evaluate whether abnormal lipid metabolism, which is responsible for a great part of membrane abnormalities found in hypertension, might be an integral part of its pathogenetic mechanisms. BLOOD PRESSUREMultiple metabolic abnormalities often accompany essential hypertension. Decreased high-density lipoproteins (HDL) together with increased plasma levels of low-density (LDL) and very low-density lipoproteins (VLDL), as well as hypertriglyceridemia, hypercholesterolemia, and insulin resistance, were found in many hypertensive patients. 3,4 There is increasing evidence for a genetic basis for the association of hypertension with insulin resistance and dyslipidemia. The genetic locus associated with dyslipidemia accompanying hypertension or diabetes seems to be closely linked to the LDL recept...

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“…From previous work it is known that a 24-h incubation with LDL increases DNA synthesis in cultured smooth arterial cells from rats [3] and humans [25]. On the assumption that the accumulated citrulline reflects NO production, we assessed LDL-induced thymidine incorporation into DNA under conditions of reduced NO synthesis using N G -methyl-L-arginine.…”

Section: Discussionmentioning

confidence: 99%

“…Apart from its physiological role as a transport vehicle and its effect on cellular cholesterol homeostasis, minor amounts of LDL have been shown to cause a general activation of human thrombocytes and vascular smooth muscle cells (VSMCs) in vitro. For example, LDL induced elevations in cytosolic free calcium concentrations and cytosolic pH, and augmented the proliferation of VSMCs from the rat [2,3]. These processes may be involved in the pathogenesis of hypertension and atherosclerosis.…”

Section: Introductionmentioning

confidence: 94%

Low‐density lipoprotein‐induced formation of nitric oxide by cultured vascular smooth muscle cells of the rat

Locher

Suter

Weisser

et al. 1997

Eur J Clin Investigation

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There is evidence that low-density lipoprotein (LDL) plays a crucial role in atherogenesis. On the cellular level, LDL has been shown to activate a number of mechanisms involved in atherogenesis and vasoconstriction. Local immoderate vasoconstriction is physiologically antagonized by nitric oxide, which is released from the endothelium. To find out whether LDL also influences the synthesis of nitric oxide in vascular smooth muscle cells, both the conversion of arginine to citrulline and the production of nitrite were determined as a measure of nitric oxide formation. After incubation of rat vascular smooth muscle cells with native LDL (25 micrograms mL-1) for 24 h, the production of both L-[14C]-citrulline [39600 (3600) cpm mg-1 cell protein] and nitric oxide [2.95 (0.56) mumol L-1] were about twice and 1.5-fold the amount of the corresponding values in untreated cells (mean +/- SD, P < 0.05, n = 4). Oxidized LDL was less effective than the native form. The presence of the arginine analogue NG-methyl-L-arginine reduced citrulline production dose-dependently but augmented DNA synthesis, both induced by LDL. In addition, the lipoprotein caused a 1.6-fold increase in cyclic GMP production following a 24-h incubation [control = 10.9 (3.8) pmol mg-1 cell protein, P = 0.016]. The results suggest that native LDL might partly impair its atherogenic potential on the vasculature by stimulating the production by smooth muscle cells of both nitric oxide and cyclic GMP.

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Effect of low-density lipoprotein on intracellular calcium, intracellular pH and DNA synthesis in cultured vascular smooth muscle cells

Cited by 11 publications

References 0 publications

Diabetes Mellitus and Hypertension, Emerging Therapeutic Perspectives

Diabetes Mellitus and Hypertension, Emerging Therapeutic Perspectives

Abnormalities of membrane function and lipid metabolism in hypertension A review

Low‐density lipoprotein‐induced formation of nitric oxide by cultured vascular smooth muscle cells of the rat

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