Vimentin regulates lung cancer cell adhesion through a VAV2-Rac1 pathway to control focal adhesion kinase activity.

Vimentin is an intermediate filament protein whose expression correlates with increased metastatic disease, reduced patient survival and poor prognosis across multiple tumor types. Despite these well-characterized correlations, the molecular role of vimentin in cancer cell motility remains undefined. To approach this, we used an unbiased phosphoproteomics screen in lung cancer cell lines to discover cell motility proteins that show significant changes in phosphorylation upon vimentin depletion. We identified the guanine nucleotide exchange factor (GEF), VAV2, as having the greatest loss of phosphorylation owing to vimentin depletion. Since VAV2 serves as a GEF for the small Rho GTPase Rac1, a key player in cell motility and adhesion, we explored the vimentin-VAV2 pathway as a potential novel regulator of lung cancer cell motility. We show that VAV2 localizes to vimentin-positive focal adhesions (FAs) in lung cancer cells and complexes with vimentin and FA kinase (FAK). Vimentin loss impairs both pY142-VAV2 and downstream pY397-FAK activity showing that vimentin is critical for maintaining VAV2 and FAK activity. Importantly, vimentin depletion reduces the activity of the VAV2 target, Rac1, and a constitutively active Rac1 rescues defects in FAK and cell adhesion when vimentin or VAV2 is compromised. Based upon this data, we propose a model whereby vimentin promotes FAK stabilization through VAV2-mediated Rac1 activation. This model may explain why vimentin expressing metastatic lung cancer cells are more motile and invasive.

[Central obesity: relationship between conicity index and lipoprotein risk factors for coronary atherosclerosis]. / Relacíon entre el índice de conicidad y los factores de riesgo lipoproteicos para la ateroesclerosis coronaria.

In middle age men the relationship between biochemical and anthropometric parameters was studied associated with central obesity in order to evaluate the risk of coronary atherosclerosis. In 31 males of 30 to 65 years of age, "apparently healthy", we determined the percentile 50 (P50) for body fat percentage (PG), 26.8% (utilizing the skinfold thicknesses) and P75 of Conicity Index (IC), 1.26. Were selected 63 subjects with different values of PG and IC. IC, adjusted for BMI and PG, correlated with Cholesterol (CT), Triglycerides (TG), CT/C-HDL, C-LDL/C-HDL, Apolipoprotein B (ApoB), Apo B/C-HDL, (P < 0.01) in all cases), and cholesterol LDL (C-LDL) (P < 0.05). This population was divided in three groups: Group I, Control, N = 19, PG < = 27% and IC < 1.26; Group II, obese without Central Obesity Predominance (POC), N = 15, PG < or = 27% and IC < or = 1.26; Group III, N = 23, obese with POC, PG > 27% and IC < or = 1.26. We found that Group III vs Group II had: CT 242 +/- 35 vs 205 +/- 40 mg/dl (P < 0.01), C-LDL 165 +/- 41 vs 138 +/- 36 mg/dl (P < 0.05) and CT/C-HDL 6.0 +/- 1.2 VS 5.1 +/- 1.2 (p < 0.05) respectively. Group III vs I showed significant differences for all biochemical parameters and index studied with exception of C-HDL. In subjects with IC > 1.26 vs IC < = 1.26 increased the frequency of coronary risk factors and indicators: CT > or = 240 mg/dl, 59% vs 12% (P < 0.001); C-LDL > or = 160 mg/dl, 55% vs 18% (P < 0.001); Apo B > 120 mg/dl, 72% vs 26% (P < 0.001); CT/C-HDL > 4.5, 86% vs 53% (P < 0.01); C-LDL/C-HDL > 3.0, 86% vs 47% (P < 0.001); Apo B/C-HDL > 2.6, 72% vs 47% (P < 0.05). Our results suggest that the use of IC combined with lipoproteic factors and index will contribute to the detection of males at risk of coronary heart disease.

[The prevalence of risk factors for coronary arteriosclerosis in the urban areas of the Argentine Patagonia. A multicenter study]. / Prevalencia de los factores de riesgo para la ateroesclerosis coronaria en zonas urbanas de la Patagonia Argentina. Estudio multicéntrico.

It is important to know the prevalence of risk factors for coronary atherosclerosis in the urban south area of Argentina in order to implement the prevention of this disease. In 330 males and 322 females of Viedma and Cipolletti (Province of Rio Negro), and Comodoro Rivadavia (Province of Chubut), we determined total cholesterol (CT), triglycerides (TG), HDL cholesterol (CHDL), LDL cholesterol (CLDL), uric acid (AcU), systolic pressure (PS), diastolic pressure (PD), cigarette smokers (Cig), and body mass index (BMI). Laboratories were coordinated as to methodology and quality control. Between 30 and 50 years of age, the prevalence of risk factors was greater in males than females; 27.3% of males vs 16.0 of females had CT > or = 240 mg/dl (p < 0.05), 30.5% vs 19.7%, had CLDL > or = 160 mg/dl (p < 0.05), 10.3% vs 5.9%, had CHDL < 35 mg/dl, 8.9% vs 4.2% had PS > 145 mmHg, 9.0% vs 5.9%, had PD > 90 mm Hg, 33.6% vs 23.4%, had Cig > or = 10/d (p < 0.05), 26.0% vs 13.8% had TG > 170 mg/dl (p < 0.05), 30.5% vs 22.4%, had BMI > 27 Kg/m2 (p < 0.05) (Figs. 2-3). This difference between sexes was not significant over 50 years of age, when the prevalence of factors increased in both sexes. In Figure 4, 41.5% of males and 34.5% of females had one primary risk factor, 13.0% of males and 9.9% of females had two factors and 1.5% of males had three. The following main combinations of two primary risk factors was observed: between 30 and 50 years of age, 10.3% of males and 3.7% of females had CLDL > or = 160 mg/dl and Cig > or = 10/d (p < 0.01); over 50 years, 19.5% of females and 11.8% of males had CLDL > or = 160 mg/dl and PS > 145 mm Hg (NS). We suggest that operatives of education for the prevention of high cholesterol, no smoking and control of high blood pressure, are needed specially in young men.

[Diet as a risk factor for coronary atherosclerosis in a rural area of Argentinian Patagonia. Comparison with the urban zone of Viedma]. / Dieta alimentaria como factor de riesgo para la ateroesclerosis coronaria en un área rural de la Patagonia argentina. Comparación con la zona urbana de Viedma.

To determine risk factors, a clinical, cardiologic, biochemical and nutritional study was carried out. A sample of the rural population of Comi-Co (N = 92), which included descendants of Mapuche indians, was compared with a sample of the urban population of Viedma (N = 94). Sheep, goat and horse meat from the rural district was analyzed. In horse meat, intramuscular fat was 1.16 g%, with 34.5% of polyunsaturated fatty acids including linolenic (18:3 w3) 11.9%, linoleic (18:2 w6) 21.0%. The diet intake of the rural population was very different from that of the urban population (p < 0.001). It contained 3420 +/- 1027 vs 2110 +/- 654 kcal, carbohydrates 40 +/- 8 vs 55 +/- 10%, lipids 33 +/- 5 vs 24 +/- 8%, proteins 28 +/- 6 vs 20 +/- 6%, cholesterol 1021 +/- 380 vs 385 +/- 156 mg/day. The rural population showed a tendency to suffer cholelithiasis. Comi-Co vs Videma males had a CHDL 53 +/- 13 vs 47 +/- 9 mg/dl (p < 0.05) and no significant differences were found between both groups when it came to blood glucose, uric acid, triglycerides and Apo B. The frequency of individuals with CT > or = 240 mg/dl, CLDL > or = 160 mg/dl, cigarettes > or = 10/day seems to be less in the rural district. In Viedma vs Comi-Co males, with any one primary factor there was a ratio of 45% vs 24% (p < 0.05). The proportion of males with two risk factors was low. No individuals with three risk factors were found.(ABSTRACT TRUNCATED AT 250 WORDS)

HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes.

BACKGROUND AND AIMS: Metabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity. DESIGN AND METHODS: Eighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated. RESULTS: As expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as >250%ml⁻¹ h⁻¹. The predictive variables of high CETP were non-HDL-C≥160mg/dl (OR=11.1;95%IC=3.3-38.2;p<0.001) and HOMA-IR>2.1 (OR=4.4;95%IC=1.3-14.8;p<0.05). CONCLUSIONS: High non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories.

Correlación entre variables asociadas con el riesgo para la aterosclerosis coronaria. I. Análisis de una muestra poblacional del sur argentino / Correlation between variable associate and the atherosclerosis coronary risk: analysis of a sample of South Argentine population

Las enfermedades cardiovasculares constituyen la primera causa de muerte en nuestro país y región. La aterosclerosis coronaria es la principal causa de la mortalidad por infarto de miocardio. Se trabajó con 330 varones y 322 mujeres "aparentemente sanas", provenientes de estudios de población realizados en Viedma, Cipolleti y Comodoro Rivadavia. En este reporte se muestran los coeficientes de correlación y la significación estadística entre los parámetros estudiados. La Edad se asoció fuertemente con BMI, PS, PD, AcU, CT y C-LDL (P<0.001).La asociación entre la Edad y PS y PD fue más significativa en mujeres que en varones. La correlación entre BMI y AcU fue más fuerte en varones que en mujeres. El consumo de cigarrillos se asoció con descensos en el C-HDL en varones (P<0.05). BMI sw asoció significativamente con PS, PD, CT, y C-LDL (P<0.001). La asociación significativa y negativa entre TG y C-HDL hallada en varones (P<0.001) y mujeres (P<0.05) debe ser tratada con mayor énfasis en la evaluación del riesgo coronario. Es necesario controlar los principales factores de riesgo para la aterosclerosis coronaria desde la juventud, sobre todo en varones, especialmente el nivel de colesterol total, el colesterol HDL, la presión sanguínea y dejar de fumar

Dieta alimentaria como factor de riesgo para la ateroesclerosis coronaria en un área rural de la Patagonia argentina: comparación con la zona urbana de Viedma / Diet as a risk factor for coronary arteriosclerosis in a rural area of Argentinian Patagonia: comparison with the urban zone of Viedma

Se realizó un estudio clínico, cardiológico, bioquímico y nutricional para determinar factores de riesgo. Se compararon individuos de un área rural, Comi-Có (N=92), en su mayoría descendientes de Mapuches, con un grupo urbano de Viedma (N=94). Se analizó la carne ovina, caprina y equina de la zona rural. La brasa intramuscular equina fue 1,16g//, con 34,5// de AG poliinsaturados (linolénico 11,9//). La dieta rural fue diferente de la urbana (p < 0,001): calorías totales 3420 ñ 1027 vs 2110 ñ 654 Kcal, hidratos carbono 40 ñ 8 vs 55 ñ 10//, lípidos 33 ñ 5 vs 24 ñ 8//, proteínas 28 ñ 9 vs 20 ñ 6//, colesterol 1021 ñ 380 vs 385 ñ 156 mg/d. Los rurales tenían tendencia a la patología biliar. Los varones de Comi-Có vs Viedma tenían C-HDL 53 ñ 13 vs 47 ñ 9 mg/dl (p < 0,05) y no se observaron diferencias en las medidas para CT, CLDL, TG, Apo B y Acido Urico. La frecuencia de: CT ò 240 mg/dl, CLDL, ò 160 mg/dl y cigarrillos ò 10/día pareció ser menor en los individuos rurales. En varones de Videma vs Como-Có con un factor principal se halló 45// vs 24// (p < 0,05). La proporción con dos factores fue baja. No se hallaron individuos con tres factores. Puede concluirse para estas muestras : 1) La dieta rica en carnes rojas del área rural patagónica no aumentó los niveles lipídicos en sangre; la frecuencia de los factores e indicadores de riesgo en la muestra rural no fue mayor que en la urbana. 2) El estilo de vida y factores étnicos podrían condicionar el efecto de la dieta sobre los lípidos sanguíneos