Subject(s)
Diabetes Mellitus/etiology , Diabetes Mellitus/immunology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , T-Lymphocytes, Regulatory/drug effects , Aging/immunology , Aging/metabolism , Cardiovascular Diseases/prevention & control , Diabetes Mellitus/classification , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Risk Factors , T-Lymphocytes, Regulatory/physiology , Terminology as TopicSubject(s)
Diabetes Mellitus, Type 2/therapy , Obesity/therapy , Overweight/therapy , Risk Reduction Behavior , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Humans , Obesity/complications , Obesity/mortality , Overweight/complications , Overweight/mortality , Treatment OutcomeABSTRACT
Although the cholesterol-heart hypothesis is often regarded as a dogmatic belief, controversy continues to surround the aetiology and pathogenesis of atherosclerosis. In fact, lowering cholesterol with statin drugs has been shown to reduce cardiovascular risk. However, statins have pleiotropic effects independent of their capacity to lower cholesterol. We highlight that statin drugs exert an important action on iron metabolism, which in turn may prevent progression and destabilization of atherosclerotic plaque. If it is found that the effect of statins on iron metabolism is a mechanism of their beneficial action, this consequence of statin use can be clinically replicated by other methods, such as controlled reduction of body iron stores. This might allow the use of lower doses or even obviate the use of statins in primary cardiovascular prevention, and therefore avoid the side effects and expense of these drugs.
Subject(s)
Atherosclerosis/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Iron/metabolism , Dose-Response Relationship, Drug , Health Care Costs , Hemosiderosis/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic useSubject(s)
Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/metabolism , 5-alpha Reductase Inhibitors/adverse effects , Animals , Breast Neoplasms/metabolism , Female , Humans , Male , Mice , Prognosis , Prostate-Specific Antigen/drug effects , Prostatic Hyperplasia/drug therapy , Prostatic Neoplasms/etiologyABSTRACT
It is well-known that cancer surgery can actually promote the growth of some tumors by a variety of mechanisms. There are observational data suggesting that surgery per se can increase the risk of cancer among individuals without a history of clinical cancer. Occult microscopic cancers are exceedingly common in the general population and are held in a dormant state by a balance between cell proliferation and cell death and also an intact host immune surveillance. The catecholamine surge from the stress of surgery and resulting ß(2)-adrenergic signaling culminates in a transient and robust increased vascular endothelial growth factor expression locally and systemically that is enough to start tumor angiogenesis and end dormancy. The same catecholamine surge and ß(2)-adrenergic signaling impairs cell-mediated immunity at a crucial time. Elegant animal studies have demonstrated that perioperative nonselective ß-blockade abrogates surgical stress-induced angiogenesis and tumor growth. Prospective human trials are desperately needed and clinical implications are discussed.
