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ADP-induced platelet aggregation in guinea pig mesenteric arterioles — an in vivo study
Monday 10 October 1994: Poster Abstracts Epidemiology stration of PLC is associated with a decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions and with a modulation of plaque cell phenotype. Overexpression of human lecithin-cholesterol acyl transferase in transgenic rabbits leads to byperalphalipoproteinemia Hoeg, Santamarina-Fojo S, Vaisman BL, Demosky SJ Jr, Hoyt RF Jr, Feldman SH, Talley G, Brewer HB Jr, Molecular Disease Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA
1
Although elevated concentrations of HDL are associated with a reduced risk for developing atherosclerosis, the underlying metabolic bases for regulating the concentrations of HDL may have different effects on atherogenesis. By the use of transgenic animals, apolipoprotein A-I and cholesteryl ester transfer protein have been shown to affect both HDL concentrations and atherosclerosis. The goal of this study was to determine if the enzyme lecithin-cholesterol acyltransferase (LCAT) was a rate-limiting step in HDL metabolism in rabbits. Embryos were harvested from superovulated New Zealand White (NZW) does. 20&600 copies of the human LCAT gene were injected into the pronuclei of embryos. A total of 512 embryos were injected, 41 kits were born and 4 founder lines were established. One of these lines integrated >I00 copies of the LCAT gene and expressed 14-17 times higher plasma LCAT activities than control NZW rabbits. This degree of LCAT overexpression had no effect on the plasma triglyceride concentrations. However, the TC HDL-C concentrations were increased 4fold and 7-fold, respectively. We conclude that plasma LCAT activity is rate-limiting in modifying HDL-C concentrations, and that hyperalphalipoproteinemia can be generated by overexpression of the LCAT gene.
1
ADP-induced platelet enteric arterioles - an uSL. Andries R, Bourgain Univ. of Brussels. Laarbeeklaan
11 aggregation in guinea pig mesin vivo stndy RH, Dept. of Physiology, Free 103, B-1090 Brussels, Belgium
Adenosine diphosphate (ADP), a potent inductor of platelet aggregation and thrombosis, has been studied extensively in vitro and in vivo for several decades. However, papers describing an in vivo method for ADP-induced platelet thrombosis at the level of the microcirculation itself were not found. The aim of this study was to investigate arterial thrombosis induced by ADP in guinea pig mesenteric arterioles 30-70pm in diameter and therefore to develop an in vivo model for precise screening of antithrombotic agents. Thrombosis was induced in vivo in the mesenteric arteriole of ig by topical superfusion by adenosine diphosphate the guinea 10J: mom, lasting 10 s) following local de-endo(ADP thelialization of the arteriolar segment by means of a small electrical current (2pA, lasting 20s). If experimental conditions remained unchanged, arteriolar thrombi could be induced every 12 mitt, repeated 10 times in succession in one segment. Using in vivo microscopy, the dynamic processes of platelet adhesion and subsequent thrombus growth, mostly followed by gradual fragmentation and/or sudden embolization at the site of the lesion, could be observed on the monitor screen. The measurements of appropriate time-dependent parameters pertaining to the thrombogenesis allowed its precise quantification. Visual inspection, confirmed by statistical analysis, demonstrated that the thrombolization-embolization phenomena in the assayed arteriolar segment were fully reproducible. In the applied experimental protocol, the arteriole served as its own control for evaluation of the effect of drug administration. The highly significant inhibition of thrombosis by antithrombotic agents was revealed by experiments where arterioles were treated with prostacyclin or its analogues. Our findings clearly indicate that other drugs and/or mediators deserve investigation by this method in order to unravel their antithrombotic properties in the microcirculation in vivo.
EPIDEMIOLOGY
El
Prevalence of obesity and lipid-related characteristics among normal young adult males in Taiwan Ding Y-A, Chen L-M, Shieh S-M, Dept. of Public Chu Nan-F= Health, National Defense Medical Center, PO Box 90048-509, Taipei, Taiwan, ROC
The prevalence of obesity among normal young adult males in Taiwan and their lipid-related characteristics were examined. After cluster sampling, 936 males (mean age 20 years, 18-24) were enrolled. The prevalence of obesity was 9.6% by the criterion of body weight greater than 20% of ideal body weight, or 12.6% by the criterion of BMI greater than 25. The obese subjects had significantly higher serum total cholesterol (C), Tg and apo B levels, and lower HDL-C than those of the non-obese. The apo A-l levels were 141.3 and 141.9 mg/dl and the Lp(a) 17.4 and 17.1 mg/dl in obese and non-obese, respcctively, the difference being not statistically significant. Pearson correlation coefficients of BMI, waist-hip ratio (WHR) and lipidrelated variables showed that both BMI and WHR are positively correlated with C, Tg and apo B but negatively correlated with HDL-C. The lipid-related variables seem more correlated with BMI than WHR. We conclude that the prevalence of obesity is slightly higher in Taiwan than in previous studies. The obese subjects had abnormal lipid metabolic characteristics such as higher cholesterol, Tg and apo B and lower HDL-C levels.
131 Cardiovascular
disease prevention in Sardinia Muntoni Sa, Muntoni S, Centro per le Malattie Dismetaboliche e I’Arteriosclerosi, 23129 Viale Merello, 09123 Cagliari, Italy
The objective of this undertaking was to implement a program of cardiovascular disease (CVD) prevention in the island of Sardinia as the last stage of a strategy developed during the last 18 years through three phases, corresponding to Targeted Projects (TP) of the Italian National Research Council (CNR). Phase 1 (CNR TP ‘ATS-RF2’, 1976-1981) was an observational survey on risk factors for CVD. Phase 2 (CNR TP ‘Ob43’, 1982-1988) was an intervention trial in experimental vs reference areas. Phase 3 is an ongoing public health action program, the ATS-Sardegna Campaign, started in 1990 as the result of scientific-political cooperation between CNR and the Sardinian Department of Health, which funds the program. As we were at Phase 3 and, moreover, Sardinia is an island with a strong regional identity, it was not considered suitable to have a reference area. Thus, the action has been spread throughout the whole island, with both the individual and population strategies. The former relies upon the General Practitioners for finding and treating high-risk subjects, The population strategy is carried out through educational messages in the newspapers and local TV, and delivery of an illustrated brochure to every Sardinian household. Evaluation is effected by comparing a wide range of pre- and post-campaign variables.
Atherosclerosis X, Montreal, Ocfober I994
1
Although elevated concentrations of HDL are associated with a reduced risk for developing atherosclerosis, the underlying metabolic bases for regulating the concentrations of HDL may have different effects on atherogenesis. By the use of transgenic animals, apolipoprotein A-I and cholesteryl ester transfer protein have been shown to affect both HDL concentrations and atherosclerosis. The goal of this study was to determine if the enzyme lecithin-cholesterol acyltransferase (LCAT) was a rate-limiting step in HDL metabolism in rabbits. Embryos were harvested from superovulated New Zealand White (NZW) does. 20&600 copies of the human LCAT gene were injected into the pronuclei of embryos. A total of 512 embryos were injected, 41 kits were born and 4 founder lines were established. One of these lines integrated >I00 copies of the LCAT gene and expressed 14-17 times higher plasma LCAT activities than control NZW rabbits. This degree of LCAT overexpression had no effect on the plasma triglyceride concentrations. However, the TC HDL-C concentrations were increased 4fold and 7-fold, respectively. We conclude that plasma LCAT activity is rate-limiting in modifying HDL-C concentrations, and that hyperalphalipoproteinemia can be generated by overexpression of the LCAT gene.
1
ADP-induced platelet enteric arterioles - an uSL. Andries R, Bourgain Univ. of Brussels. Laarbeeklaan
11 aggregation in guinea pig mesin vivo stndy RH, Dept. of Physiology, Free 103, B-1090 Brussels, Belgium
Adenosine diphosphate (ADP), a potent inductor of platelet aggregation and thrombosis, has been studied extensively in vitro and in vivo for several decades. However, papers describing an in vivo method for ADP-induced platelet thrombosis at the level of the microcirculation itself were not found. The aim of this study was to investigate arterial thrombosis induced by ADP in guinea pig mesenteric arterioles 30-70pm in diameter and therefore to develop an in vivo model for precise screening of antithrombotic agents. Thrombosis was induced in vivo in the mesenteric arteriole of ig by topical superfusion by adenosine diphosphate the guinea 10J: mom, lasting 10 s) following local de-endo(ADP thelialization of the arteriolar segment by means of a small electrical current (2pA, lasting 20s). If experimental conditions remained unchanged, arteriolar thrombi could be induced every 12 mitt, repeated 10 times in succession in one segment. Using in vivo microscopy, the dynamic processes of platelet adhesion and subsequent thrombus growth, mostly followed by gradual fragmentation and/or sudden embolization at the site of the lesion, could be observed on the monitor screen. The measurements of appropriate time-dependent parameters pertaining to the thrombogenesis allowed its precise quantification. Visual inspection, confirmed by statistical analysis, demonstrated that the thrombolization-embolization phenomena in the assayed arteriolar segment were fully reproducible. In the applied experimental protocol, the arteriole served as its own control for evaluation of the effect of drug administration. The highly significant inhibition of thrombosis by antithrombotic agents was revealed by experiments where arterioles were treated with prostacyclin or its analogues. Our findings clearly indicate that other drugs and/or mediators deserve investigation by this method in order to unravel their antithrombotic properties in the microcirculation in vivo.
EPIDEMIOLOGY
El
Prevalence of obesity and lipid-related characteristics among normal young adult males in Taiwan Ding Y-A, Chen L-M, Shieh S-M, Dept. of Public Chu Nan-F= Health, National Defense Medical Center, PO Box 90048-509, Taipei, Taiwan, ROC
The prevalence of obesity among normal young adult males in Taiwan and their lipid-related characteristics were examined. After cluster sampling, 936 males (mean age 20 years, 18-24) were enrolled. The prevalence of obesity was 9.6% by the criterion of body weight greater than 20% of ideal body weight, or 12.6% by the criterion of BMI greater than 25. The obese subjects had significantly higher serum total cholesterol (C), Tg and apo B levels, and lower HDL-C than those of the non-obese. The apo A-l levels were 141.3 and 141.9 mg/dl and the Lp(a) 17.4 and 17.1 mg/dl in obese and non-obese, respcctively, the difference being not statistically significant. Pearson correlation coefficients of BMI, waist-hip ratio (WHR) and lipidrelated variables showed that both BMI and WHR are positively correlated with C, Tg and apo B but negatively correlated with HDL-C. The lipid-related variables seem more correlated with BMI than WHR. We conclude that the prevalence of obesity is slightly higher in Taiwan than in previous studies. The obese subjects had abnormal lipid metabolic characteristics such as higher cholesterol, Tg and apo B and lower HDL-C levels.
131 Cardiovascular
disease prevention in Sardinia Muntoni Sa, Muntoni S, Centro per le Malattie Dismetaboliche e I’Arteriosclerosi, 23129 Viale Merello, 09123 Cagliari, Italy
The objective of this undertaking was to implement a program of cardiovascular disease (CVD) prevention in the island of Sardinia as the last stage of a strategy developed during the last 18 years through three phases, corresponding to Targeted Projects (TP) of the Italian National Research Council (CNR). Phase 1 (CNR TP ‘ATS-RF2’, 1976-1981) was an observational survey on risk factors for CVD. Phase 2 (CNR TP ‘Ob43’, 1982-1988) was an intervention trial in experimental vs reference areas. Phase 3 is an ongoing public health action program, the ATS-Sardegna Campaign, started in 1990 as the result of scientific-political cooperation between CNR and the Sardinian Department of Health, which funds the program. As we were at Phase 3 and, moreover, Sardinia is an island with a strong regional identity, it was not considered suitable to have a reference area. Thus, the action has been spread throughout the whole island, with both the individual and population strategies. The former relies upon the General Practitioners for finding and treating high-risk subjects, The population strategy is carried out through educational messages in the newspapers and local TV, and delivery of an illustrated brochure to every Sardinian household. Evaluation is effected by comparing a wide range of pre- and post-campaign variables.
Atherosclerosis X, Montreal, Ocfober I994