Actividades paraoxonasa y arilesterasa bajas en sujetos mexicanos con enfermedad arterial coronaria / Low paraoxonase and arylesterase plasma activities in mexican patients with coronary artery disease

PURPOSE: To determine the Paraoxonase-1 (PON1) activity as well as its pheno- and genotypes at position 192 in Mexican subjects with diagnosis of coronary heart disease (CHD). METHODS: We determined the PON1-192 polymorphism by PCR-RFLP, and serum PON1 activity, using either paraoxon (PONase activity) or phenylacetate (ARE activity) as substrates, in 155 clinically healthy individuals (control group), and 155 patients with at least one myocardial infarction (CHD group). The biochemical A/B phenotype was determined by the ratio of the NaCI 1 M-stimulated PONase activity divided by the ARE activity. RESULTS: We found significantly lower PONase and ARE activities in CHD patients as compared to controls (233.1 +/- 102.1 vs. 295.8 +/- 159.1 nmol/min/mL, and 103.1 +/- 33.7 vs 220.2 +/- 120.7 micromol/min/mL, respectively, p<0.05 for both). Allele and genotype frequencies for PON1-192 were similar in CHD patients and healthy controls. Moreover, in the control group, the PON1-192 Q/R genotype did not matched with the A/B phenotype as has been proposed by other studies. CONCLUSIONS: There were important differences in the ARE and PONase activities between Mexican CHD patients and controls, suggesting that PON1 activity could be a good marker of CHD risk, whereas PON1-192 lacks of value to assess such risk.

[Low paraoxonase and arylesterase plasma activities in Mexican patients with coronary artery disease]. / Actividades paraoxonasa y arilesterasa bajas en sujetos mexicanos con enfermedad arterial coronaria.

PURPOSE: To determine the Paraoxonase-1 (PON1) activity as well as its pheno- and genotypes at position 192 in Mexican subjects with diagnosis of coronary heart disease (CHD). METHODS: We determined the PON1-192 polymorphism by PCR-RFLP, and serum PON1 activity, using either paraoxon (PONase activity) or phenylacetate (ARE activity) as substrates, in 155 clinically healthy individuals (control group), and 155 patients with at least one myocardial infarction (CHD group). The biochemical A/B phenotype was determined by the ratio of the NaCI 1 M-stimulated PONase activity divided by the ARE activity. RESULTS: We found significantly lower PONase and ARE activities in CHD patients as compared to controls (233.1 +/- 102.1 vs. 295.8 +/- 159.1 nmol/min/mL, and 103.1 +/- 33.7 vs 220.2 +/- 120.7 micromol/min/mL, respectively, p<0.05 for both). Allele and genotype frequencies for PON1-192 were similar in CHD patients and healthy controls. Moreover, in the control group, the PON1-192 Q/R genotype did not matched with the A/B phenotype as has been proposed by other studies. CONCLUSIONS: There were important differences in the ARE and PONase activities between Mexican CHD patients and controls, suggesting that PON1 activity could be a good marker of CHD risk, whereas PON1-192 lacks of value to assess such risk.

Decreased activity of lecithin:cholesterol acyltransferase and hepatic lipase in chronic hypothyroid rats: implications for reverse cholesterol transport.

Chronic hypothyroidism is frequently associated with atherosclerosis due to increased cholesterol plasma levels; nevertheless, the contribution of impaired reverse cholesterol transport (RCT) in this process has not been completely elucidated. The aim of this study was to evaluate the effect of thyroidectomy (Htx) upon the main stages of RCT in rats. Plasma lipid alterations induced by thyroidectomy showed a slight, but significant, reduction of total plasma triglycerides, a 300% increase of LDL-cholesterol and a 25% decrease in HDL-cholesterol compared to control rats. We evaluated the first stage of RCT determining 3H-cholesterol efflux in Fu5AH cells. The capacity of HDL obtained from Htx rats to promote cholesterol efflux was similar to that of controls. Lecithin:cholesterol acyltransferase (LCAT) activity, the second stage and the driving force of RCT was 30% lower in Htx animals compared to controls, as determined by reconstituted HDL used as an external substrate. Lipoproteins are remodeled by hepatic lipase; the mean activity of this enzyme in postheparin plasma of Htx animals was reduced by 30% compared to controls, thus suggesting an impaired HDL remodeling by this enzyme in the hypothyroid status. In contrast, lipoprotein lipase activity in the Htx group was unchanged. In summary, this study demonstrates that chronic hypothyroidism in the rat induced an impaired RCT mainly at the cholesterol esterification, and HDL remodeling mediated by hepatic lipase. The latter probably results in an abnormal HDL structure, i.e. phospholipid enrichment, which contributes to decrease HDL-apo AI fractional catabolic rates.