Gene-environment interaction in hypertension, stroke and atherosclerosis in experimental models and supportive findings from a world-wide cross-sectional epidemiological survey: a WHO-cardiac study.
1. Genetic rat models of hypertension, such as spontaneously hypertensive rats (SHR) and in particular, stroke-prone SHR (SHRSP) are useful models for research on the genetic pathogenesis, gene-environment interaction and control of environmental factors for the prevention of hypertension and related cardiovascular diseases (CVD). 2. Since recent genetic analysis of hypertension in SHRSP indicated that one of the hypertensive genes related to salt-induced blood pressure (BP) rise was linked with the gene of the angiotensin-converting enzyme, gene-environment interaction is important in the humoral, neural, vascular and nutritional mechanisms of hypertension and CVD. 3. Extensive experimental studies in SHRSP by the authors have demonstrated nutritional factors counteracting directly or indirectly against the adverse effect of excess salt intake, such as K, Mg, Ca, dietary fibres, protein, some amino acids and fatty acids, etc.; they are therefore effective in preventing stroke, the typical complication of hypertension. 4. Experimental atherosclerotic models were established in SHRSP, which indicated also a gene-environment interaction in the pathogenesis of atherosclerosis at the cellular level of vascular smooth muscle cells. Excess salt intake accelerated cholesterol absorption from the intestine to induce arterial fat deposition as well as to active platelet aggregation by the mechanism of increased intracellular Ca2+ mobilization. 5. Based on such experimental findings on the hypertension and related CVD prevention, a cross-sectional multicentre epidemiological 'CVD and Alimentary Comparison' Study (WHO-CARDIAC Study) was designed to assess the relationship of biological markers of dietary factors with BP ('core' study) and major CVD mortalities ('complete' study) and has been successfully undertaken for the past 8 years in co-operation with 54 centres in 23 countries. 6. The results of 'core' study so far obtained by cross-centre simple linear regression analysis demonstrated adverse effects of body mass index and salt intake on BP in men and possible beneficial effects of Mg by within-centre multiple linear regression analysis. 7. Preliminary cross-centre simple linear regression analysis of the 'complete' study indicated a positive correlation of serum cholesterol levels and negative correlation of serum phospholipid poly-unsaturated to unsaturated fatty acid ratios and 24 h urinary taurine excretion with coronary heart diseases mortality; a positive correlation of 24 h urinary Na and Na/K ratios and a negative correlation of serum cholesterol levels with stroke mortalities was indicated. 8. These epidemiological data confirmed mostly the applicability of experimental findings to the nutritional prevention of hypertension and CVD prevention.(ABSTRACT TRUNCATED AT 400 WORDS)
Yamori
Y
Y
WHO Collaborating Center for Research on Primary Prevention of Cardiovascular Diseases, Izumo, Japan.
Nara
Y
Y
Mizushima
S
S
Murakami
S
S
Ikeda
K
K
Sawamura
M
M
Nabika
T
T
Horie
R
R
D000818:Animals; D001161:Arteriosclerosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D004777:Environment; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D051381:Rats; D014944:World Health Organization