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Biomedical subjects

M Viñals

Publications and source records attributed to M Viñals.

16 recordsLinked to original sources
PubMed2001

Role of SR-BI in regulating lipoprotein structure and metabolism.

The scavenger receptor class B type I (SR-BI) is a cell surface lipoprotein receptor that mediates physiologically relevant selective cholesteryl ester uptake from high-density lipoprotein (HDL). SR-BI appears to be required for the maintenance of reverse cholesterol transport, normal HDL levels and HDL structure by means of hepatic-selective HDL-cholesterol and phospholipid uptake in mice. SR-BI can also promote the selective uptake of cholesteryl ester from apoB-containing lipoproteins; however, unlike the effect of SR-BI on HDL-cholesterol, the effect on low-density lipoprotein is limited in vivo. Furthermore, SR-BI plays a protective role against atherosclerotic development. A pharmacological agent that increased reverse cholesterol transport by targeting SR-BI could become a powerful tool for prevention of or therapeutic intervention in atherosclerotic cardiovascular diseases.

Journal Article↗
PubMed1999

Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology.

The high density lipoprotein (HDL) receptor SR-BI (scavenger receptor class B type I) mediates the selective uptake of plasma HDL cholesterol by the liver and steroidogenic tissues. As a consequence, SR-BI can influence plasma HDL cholesterol levels, HDL structure, biliary cholesterol concentrations, and the uptake, storage, and utilization of cholesterol by steroid hormone-producing cells. Here we used homozygous null SR-BI knockout mice to show that SR-BI is required for maintaining normal biliary cholesterol levels, oocyte development, and female fertility. We also used SR-BI/apolipoprotein E double homozygous knockout mice to show that SR-BI can protect against early-onset atherosclerosis. Although the mechanisms underlying the effects of SR-BI loss on reproduction and atherosclerosis have not been established, potential causes include changes in (i) plasma lipoprotein levels and/or structure, (ii) cholesterol flux into or out of peripheral tissues (ovary, aortic wall), and (iii) reverse cholesterol transport, as indicated by the significant reduction of gallbladder bile cholesterol levels in SR-BI and SR-BI/apolipoprotein E double knockout mice relative to controls. If SR-BI has similar activities in humans, it may become an attractive target for therapeutic intervention in a variety of diseases.

Animals↗
PubMed1999

Regulatory effects of HDL on smooth muscle cell prostacyclin release.

One mechanism by which high density lipoproteins (HDLs) exert their protective effect against coronary artery disease could be related to the induction of prostacyclin (PGI(2)) release in the vessel wall. We have recently shown that HDL increases PGI(2) production in rabbit smooth muscle cells (RSMCs) and that this increase is dependent on cyclooxygenase-2 (Cox-2). Here we analyze the mechanism by which rabbit HDL induces PGI(2) release in RSMCs. Our results show that although HDL(2) and HDL(3) share a similar capacity to induce Cox-2 protein levels, HDL(3) stimulates a higher PGI(2) release than does HDL(2), probably because of their relative arachidonate contents. Acetylsalicylic acid pretreatment (300 micromol/L, 30 minutes) significantly reduced the HDL-induced PGI(2) release, suggesting that both preexisting and induced Cox-2 activities were involved in the HDL effect. Ca(2+)-dependent cytosolic phospholipase A(2) (cPLA(2)) and Cox-1 protein levels were not altered by HDL. Dexamethasone (2 micromol/L), which also inhibited the HDL-induced PGI(2) release, reduced significantly both Cox-2 mRNA and protein levels without affecting cPLA(2) and Cox-1 protein levels. In addition, methylarachidonyl fluorophosphonate, a potent inhibitor of cPLA(2), did not produce any effect on HDL-induced PGI(2) release. In the presence of cycloheximide, Cox-2 mRNA levels were induced by HDL and inhibited by dexamethasone, suggesting that HDL and dexamethasone work in the absence of de novo protein synthesis. These results indicate an early effect of HDL on PGI(2) biosynthesis, specifically increasing Cox-2. PD98059, an inhibitor of mitogen-activated protein kinase kinase, completely inhibited HDL-induced PGI(2) release, whereas GF109203X, a protein kinase C inhibitor, had no effect. Thus, HDL induces PGI(2) synthesis by a mechanism dependent on the mitogen-activated protein kinase pathway but independent of protein kinase C.

Animals↗
PubMed1997

Mevalonate deprivation impairs IGF-I/insulin signaling in human vascular smooth muscle cells.

3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors (statins) are therapeutically used to lower plasma cholesterol levels. In addition, these drugs can block vascular smooth muscle cell (VSMC) proliferation. The present study addressed the question whether the inhibitory effect of lovastatin on premitotic DNA synthesis correlates with a downregulation of c-fos mRNA levels, a marker of signaling efficiency, in human SMC. Here we show that in human SMC exposed to individual growth factors (platelet-derived growth factor, epidermal growth factor, alpha-thrombin, insulin, insulin-like growth factor I (IGF-I)) and human serum, the maximal [3H]thymidine incorporation and c-fos mRNA expression are closely correlated. Only alpha-thrombin elicited overexpression of c-fos as compared with its effect on [3H]thymidine incorporation. Lovastatin efficiently inhibited [3H]thymidine uptake promoted by all mitogens tested (76-87%); however, it significantly inhibited upregulation of c-fos mRNA levels induced only by insulin (33-67%, P < 0.05) and IGF-I (31 57%, P < 0.05). This inhibition was overcome by mevalonate and geranylgeraniol, and partially by farnesol. c-fos mRNA expression induced by 4-beta-phorbol-12-myristate-13-acetate, an activator of protein kinase C, was insensitive to lovastatin treatment. Thus, in human vascular SMC, lovastatin impairs premitotic DNA synthesis induced by growth factors, but only c-fos expression promoted by insulin and IGF-I. These data indicate that statin-sensitive and -insensitive pathways seem to be involved in the regulation of c-fos in the response of human SMC to proliferative stimuli, and suggest a prominent role of isoprenylated proteins in the activation of VSMC through the IGF-I/insulin dependent pathways.

Cells, Cultured↗
PubMed1997

HDL-induced prostacyclin release in smooth muscle cells is dependent on cyclooxygenase-2 (Cox-2).

Cyclooxygenase-1 (Cox-1) and Cox-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. We studied the effects of plasma HDL and LDL on the synthesis of prostacyclin, Cox-1/Cox-2 mRNA, and protein expression by rabbit aortic smooth muscle cells. Prostacyclin synthesis was measured by enzyme immunoassay (EIA) of the stable metabolite of prostacyclin (PGI2), 6-ketoprostaglandin F1 alpha. HDL (150 micrograms/mL) induced release of PGI2 to values 3.46 +/- 0.3-fold above control. Incubations with LDL did not induce release of PGI2. N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS-398), a selective irreversible Cox-2 inhibitor, blocked the HDL-induced PGI2 synthesis. Cycloheximide, actinomycin D, and dexamethasone downregulated HDL-induced PGI2 synthesis; therefore, HDL induced de novo synthesis of protein and Cox-2 mRNA. In addition, Northern blot analyses did not reveal differences in Cox-1 mRNA levels between control and HDL-treated cells, whereas Cox-2 mRNA levels were significantly increased in treated cells. Western blot analysis also showed an increase in the levels of Cox-2 protein. Therefore, the effects of HDL on PGI2 synthesis are mediated via upregulation of Cox-2 expression.

Amino Acid Sequence↗
PubMed1994

[Posterior cortical dementia].

Two patients, aged 59 and 73 years, presented with the clinical syndrome of Posterior Cortical Dementia (PCD). Follow-up during 3 and 11 years confirmed the progressive nature of the disorder. Posterior cerebral impairment was seen on SPECT studies. Neuroimaging studies showed an early dilatation of the right occipital ventricular horn which predominated over the cortical atrophy. This kind of cerebral atrophy could identify a subset of PCD cases that may be unrelated to Alzheimer's disease.

Aged↗
PubMed1993

Fibrates modify rat hepatic fatty acid chain elongation and desaturation in vitro.

Three fibric acid derivatives, clofibric acid (CFB), bezafibrate (BFB), and gemfibrozil (GFB), mainly used in the treatment of hypertriglyceridaemic or mixed hyperlipidaemic states, have been tested for their ability to modify fatty acid chain elongation and desaturation in vitro. Both endogenous and exogenous (saturated, monounsaturated and polyunsaturated) fatty acid elongations were inhibited by fibrates at concentrations well within the physiological range (IC50 values for GFB were between 0.1 and 0.3 mM). The potency order was GFB > BFB > CFB. Inhibition was not due to an impairment of the activation step from free fatty acids to acyl-CoAs, as palmitoyl-CoA synthetase was only slightly inhibited (IC50 value for GFB = 2.8 mM). Fibrates (GFB) appeared to behave as mixed non-competitive inhibitors with respect to malonyl-CoA when the rate limiting step of elongation, the condensing enzyme, is assayed. Further, delta 6 and delta 5 desaturates were inhibited by the three drugs (GFB > BFB > CFB), although not to the same extent as the elongation system. In contrast, delta 9 desaturase activity was not affected by fibrates.

Acetyltransferases↗
PubMed1993

Cytosolic lipogenic enzymes: effect of fibric acid derivatives in vitro.

The effect of fibric acid derivatives, clofibric acid (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on hepatic cytosolic enzymatic activities involved in saturated fatty acid synthesis has been estudied in vitro. From all the activities tested (fatty acid synthetase, acetyl-CoA carboxylase, ATP-citrate lyase, malic enzyme, malic dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase), only acetyl-CoA carboxylase and glucose-6-phosphate dehydrogenase were significantly inhibited by fibrates, with the following order of potency: GFB > BFB > > CFB. The characteristics of the inhibition phenomena (IC50, kinetic analysis, time and protein dependence, etc) and their transcendence to the effects of fibric acid derivatives in vivo are discussed.

Animals↗
PubMed1992

Inhibition of rat liver microsomal fatty acid chain elongation by gemfibrozil in vitro.

Gemfibrozil, a hypolipidemic drug mainly used in the treatment of hypertriglyceridemic states, strongly inhibits the rat hepatic microsomal fatty acid chain elongation system in vitro. The inhibition is independent on the reducing cofactor used in the assay. Furthermore, gemfibrozil seems to act by inhibiting the rate-limiting step of the elongation process, the condensing reaction, without discriminating among the proposed three different condensing enzymes, devoted to condensation of saturated, mono-unsaturated and polyunsaturated acyl-CoA substrates.

Animals↗
PubMed1992

[Dystonia sensitive to levodopa].

A Spanish family with the DTI variant sensitive to L-Dopa is presented with three patients, 2 first cousins and an aunt being described. The dystonic beginning of the disease during infancy is of note in the former two patients as is the later initiation of parkinsonism in the third patient. Marked improvement was observed in all of the patients with L-Dopa treatment. Some peculiarities of the cases are commented upon and the discussion includes analysis of the nosological aspects, relation with juvenile parkinsonism and Parkinson's disease. Finally, reference is made to the different hypersensitivity for presenting choreic dyskinesia which the patients had.

Adult↗
PubMed1991

[The management by medical treatment of an intracranial mycotic aneurysm in a patient with infectious endocarditis with negative blood cultures and hypertrophic myocardiopathy].

A case of intracranial mycotic aneurysm due to culture-negative infective endocarditis involving a patient with hypertrophic cardiomyopathy is reported. The patient, a 22-year-old woman with no history of known prior disease, had fever, headache and focal neurologic symptoms 3 days before admission. An echocardiogram performed after admission disclosed an obstructive hypertrophic cardiomyopathy and a gross vegetation on septal leaflet of mitral valve. Cerebral angiography revealed a mycotic aneurysm involving a peripheral branch of the left middle cerebral artery. Causal agent was not identified, and empiric treatment with penicillin G and streptomycin achieved medical cure and disappearance of the aneurysm 2 weeks later. Four months after endocarditis had been cured, the patient was electively operated because of progression of mitral regurgitation. Six months later, she is asymptomatic.

Adult↗
PubMed1989

[Recurrent Miller-Fisher syndrome associated with brachial neuritis].

The clinical and electrophysiological evolution of a 24-year-old patient with Miller-Fisher's syndrome and findings of mild peripheral neuropathy in the electromyographic study is reported. The patient had been treated six years previously for a similar disease and he recovered in 2 months. During the plasmapheresis therapy of the second episode he developed pain and weakness of the left shoulder girdle, and the EMG was consistent with bilateral brachial neuritis. The disease had improved clinically after 6 weeks, except for supracapsular brachial neuropathy; this territory remained denervated after 3 months of evolution. A diagnosis of Crohn's disease had been made between both episodes. The discussion focuses on the rarity of recurrent forms of Miller-Fisher's syndrome and the association of the reported case with brachial neuritis and Crohn's disease.

Adult↗