Human diseases atherosclerosis

M. Nordstrom and T. Kjellstrom, Age dependency of cystathione beta-synthase activity in human fibroblasts in homocysteinemia and atherosclerotic vascular disease. Atherosclerosis 94, 213-221 (1992). 

Nuclear factor kappa B (NF-kB) serves as a central regulator of the human immune and inflammatory response, and is a family of inducible transcription factors found virtually ubiquitously in all cells and functions in a variety of human diseases including those related to inflammation, cancer, asthma, atherosclerosis, AIDS, septic shock, and arthritis. Due to its role in a wide variety of diseases, NF-kB has become one of the major targets for drug development. Inhibition of NF-kB activity potentially contributes to cancer chemoprevention [27,28]. 

Cardiovascular disease models demonstrate aspects/features of humanized disease models. For hyperlipidemia-based atherosclerosis, there is a lack of a spontaneous in vivo mouse model because mice are resistant to (diet-induced) hyperlipidemia. Therefore a number of transgenic mice have been developed to better understand the pathogenesis in humans and obtain mouse models predictive of the human disease. Overexpression of ApoB, ApoE-variants, and knockout of ApoE, the LDL receptor or LPL (lipopro-... 

These form a large, unrelated group of disorders which underlie a variety of human diseases. The immune system is often involved with inflammatory disorders, demonstrated in both allergic reactions and some myopathies. Non-immune diseases with aetiological origins in inflammatory processes are thought to include cancer, atherosclerosis (Chapter 5) and ischaemic heart disease. 

Abstract Inflammation induces oxidative stress, lipid and protein oxidation and modifies redox equilibrium. At the whole body level, inflammation and oxidative stress contribute to the pathogenesis of many human diseases including atherosclerosis, and related cardiovascular diseases, leading cause of morbidity and mortality in Western countries. 

An abundance of food has obvious consequences it promotes our specific appetites. Lipids account for about 40% of the calories ingested in Western countries, whereas nutritional recommendations are 5-10% lower. This excessive lipid intake, associated with a qualitative imbalance (excess of saturated fatty acids and cholesterol, too high to6/to3 ratio) strongly favours the development of obesity and associated diseases (atherosclerosis, non insulin-dependent diabetes, hypertension, cancer). This attraction to fatty foods is not specific to humans. Rats and mice spontaneously prefer lipid-rich foods if provided with a free choice (Tsuruta et al. 1999 Takeda et al. 2000). This attraction to lipids is so strong that mice given free access to an oil as an optional diet rapidly become obese (Takeda et al. 2001a). The origin of this preference for lipids remains unclear. 

Unregulated cholesterol production can lead to serious human disease. When the sum of cholesterol synthesized and cholesterol obtained in the diet exceeds the amount required for the synthesis of membranes, bile salts, and steroids, pathological accumulations of cholesterol in blood vessels (atherosclerotic plaques) can develop, resulting in obstruction of blood vessels (atherosclerosis). Heart failure due to occluded coronary arteries is a leading cause of death in industrialized societies. Atherosclerosis is linked to high levels of cholesterol in the blood, and particularly to high levels of LDL-bound cholesterol there is negative correlation between HDL levels and arterial disease. 

DHEA is dehydroepiandrosterone. It is a plant derivative of a hormone from the Mexican wild yam. It is naturally produced by the adrenals and is one of the most abundant hormones in humans. It begins at age 7 and peaks around 30 years of age. As a supplement, it promises to enhance metabolic functions, increase energy, control stress, maintain proper mineral levels, balance the production of hormones, fight aging, improve memory, build body muscle, and reduce fat. It supposedly reduces the risk of cancer, heart disease, atherosclerosis, Alzheimer s disease, and schizophrenia. Many scientists claim this supplement is useless. 

Halliwell, B. (1989). Free radieal s, reactive oxygen species and human disease a critical evaluation with special reference to atherosclerosis. Brit. J. Exp. Pathology, 70(6), 737. 

The pig is generally accepted and widely used as an animal model for human disease. The domestic pig has found favor with scientists in the study of spontaneous and induced atherosclerosis and particularly the pathogenesis of control of this condition. For a review on the suitability and limitations of the pig as an animal model see the reference by Dodds (1982). 

---