arginine and statins

those of you that have followed my ruminations on cholesterol, statins, and citrulline know that i believe that atherosclerosis is not something that just happens when you reach 55 but is a gradual process of placque deposition over many years. the message here is to do something about it when you are younger and still can since it is very difficult to reverse the process.
i have been a fan of l-citrulline for its modulation of the NOS pathway and all that implys and here is an interesting article about reversing buildup and the use of arginine or citrulline.

jb

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Ann Biol Clin (Paris). 2005 Sep-Oct;63(5):443-55.

[Arginine and statins: relationship between the nitric oxide pathway and the atherosclerosis development]
[Article in French]

Rasmusen C, Cynober L, Couderc R.

Laboratoire de biologie de la nutrition EA2498, Faculté de Pharmacie Paris 5. [email protected]

Abstract
Arginine, a semi-essential amino acid, plays a major nutritional and metabolic role. In particular, arginine is the precursor of nitric oxide which is involved in the endothelial function. Several factors, such as hypercholesterolemia, diabetes, ageing and hypertension are established risk factors for atherosclerosis, in particular by decreasing the availability of nitric oxide. Thus, endothelial nitric oxide synthase has a pivotal role against atherosclerosis. A suitable amount of cofactor and a sufficient intake of arginine have been shown to modulate nitric oxide-induced vasodilatation: despite the fact that the intracellular concentration of arginine is well above the Km of endothelial nitric oxide synthase, an arginine supplemented-diet is effective in increasing the production of nitric oxide. Several mechanisms have been proposed to explain this "arginine paradox": co-localization of the arginine transporter with endothelial nitric oxide synthase, intracellular arginine regeneration from citrulline, balance between endothelial arginase and nitric oxide synthase. Statins which are HMG-CoA reductase inhibitors inhibit the synthesis of mevalonate, and thus that of cholesterol. In addition, statins increase the stabilization of endothelial nitric oxide synthase mRNA. The co-operation between cholesterol synthesis and the upregulation of caveolin-1 on the one hand, and the activation of endothelial nitric oxide synthase on the other hand, is very tight. A depletion of cholesterol in the caveolae induces a decrease in caveolin-1 at the cell surface allowing NOS activation. Thus statins improve nitric oxide production and vasodilatation. In a recent work in the hypercholesterolemic Watanabe rabbit, we have demonstrated that the combination of arginine with a statin, namely atorvastatin, significantly hinders the spreading of atherosclerotic plaques as compared with monotherapies. Such association of a nutriment and a drug open a new area of therapeutic strategy.