Homocysteine inflammation

Goldstein, L.B., 2000. Novel risk factors for stroke homocysteine, inflammation, and infection. Current Atherosclerosis Reports.4. 

In addition to the five major risks, the ATP III guidelines recognize other factors that contribute to CHD risk. These are classified as life-habit risk factors and emerging risk factors. Life-habit risk factors, consisting of obesity, physical inactivity, and an atherogenic diet, require direct intervention. For example, emerging risk factors are lipoprotein(a), homocysteine, prothrombotic/proinflammatory factors, and C-reactive protein (CRP). C-reactive protein is a marker of low-level inflammation and appears to help in... 

In this new scenario much attention is being paid to the investigation of a series of markers of inflammation as reliable indicators of coronary risk. Their value is stressed by the observation that up to one third of events occurs in subjects without traditional risk factors. The C-reactive protein (CRP) seems to provide the strongest risk prediction for CHD in women (Albert 2000 Ridker 2001), although homocysteine, interleukin-6 (IL-6), and lipoprotein (a) [ Lp (a) ], among others, have each been independently associated with increased risk for CHD in women (for a review see Davison and Davis 2003 Rader 2000). 

Increases in plasma S-AA levels have previously been reported in patients with coronary disease (57). S-AA and plasma intracellular adhesion molecule-1 were elevated in patients with CAD and hyperhomocysteinemia, but only S-AA decreased after vitamin supplementation (35). Homocysteine activates nuclear factor- in endothelial cells, possibly via oxidative stress (58), and increases monocyte chemoattractant protein-1 expression in vascular smooth muscle cells (59). Additionally, it stimulates interleukin-8 expression in human endothelial cultures (60). These inflammatory factors are known to participate in the development of atherosclerosis. Taken together, these reports suggest an association of elevated tHcy and low-grade inflammation in CAD. 

To conclude, hyperhomocysteinemia is associated with oxidative stress, inflammation, endothelial dysfunction, and dysfunction of coagulation in animals and in humans, but vitamin supplementation does not consistently normalize these changes in spite of large reductions in homocysteine. It still remains be seen whether homocysteine per se causes the pathological processes or whether it is simply an innocent bystander. 

Is homocysteine involved in the pathogenesis of restenosis An association between homocysteine and restenosis is not unlikely, given the fact that homocysteine appears to induce inflammation, impair endothelial function, and stimulate smooth muscle proliferation all these mechanisms are potentially implicated in the development of restenosis. However, the data regarding tHcy levels and the risk of restenosis after coronary angioplasty are conflicting. Some investigators found an increased risk of restenosis after PCI in patients with high plasma levels of homocysteine, especially in patients not treated with stents (70-72), whereas others did not find any increased risk either in patients with (73-75) or without stents (76). 

Jonasson T, et al. Plasma homocysteine and markers for oxidative stress and inflammation in patients with coronary artery disease-a prospective randomized study of vitamin supplementation, Clin Chem Lab Med 2005 43(6) 628-634. 

Homocysteine-lowering treatment with folic acid, cobalamin and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction or hypercoagulability in patients with previous transient ischemic attack or stroke a randomized substudy of the VITATOPS trial. Stroke 36 144-146... 

The response-to-injury hypothesis states that risk factors such as oxidized LDL, mechanical injury to the endothelium (e.g., percutaneous transluminal angioplasty), excessive homocysteine, immunologic attack, or infection-induced (e.g.. Chlamydia, herpes simplex virus 1) changes in endothelial and intimal function lead to endothelial dysfunction and a series of cellular interactions that culminate in atherosclerosis. C-reactive protein (CRP) is an acute-phase reactant and a marker for inflammation it may be useful in identifying patients at risk for developing CAD. The eventual outcomes of this atherogenic cascade are clinical events such as angina, MI, arrhythmias. 

Greany, K.A. J.A. Netdeton K.E. Wangen W. Thomas M.S. Kurzer. Consumption of isoflavone-rich soy protein does not alter homocysteine ot markers of inflammation in postmenopausal women. Eur. J. Clin. Nutr. 2007, Sep 5 [Epub ahead of print]. 

Besides their extraordinary assistance with stress and depression, Bs help the brain transform amino acids into such neurotransmitters as serotonin, norepinephrine, and dopamine. And they keep your body from making too much homocysteine, a potentially harmful substance that can promote inflammation. You can simply take a B-complex, or focus on the following B vitamins ... 

Figure 3.2 Beneficial effects of folic acid on vascular wall. Folic acid circulates in human body as 5-methyltetrahydrofolate (5-MTHF). 5-MTHF lowers circulating homocysteine (Hey) levels, thus reducing systemic oxidative stress and Hcy-induced activation of prothrombotic mechanisms. In addition, vascular 5-MTHF has a favourable effect on intracellular Hey metabolism, attenuating Hcy-induced activation of NADPH oxidase isoforms (NOXs) in the vascular wall. Furthermore vascular 5-MTHF scavenges per se peroxynitrite (ONOO ) radicals in the vascular wall preventing the oxidation of vascular tetrahydrobiopterin (BH4) associated with endothelial nitric oxide synthase (eNOS) uncoupling and diminished vascular nitric oxide (NO) bioavailability. In total through these effects 5-MTHF lowers vascular oxidative and nitrosative stress. Thus by modulating vascular redox, 5-MTHF inhibits activation of proinffammatory pathways which orchestrate vascular wall inflammation and perpetuate endothelial dysfunction and atherogenesis development (unpublished).

S. Friso, P.F. Jacques, P.W. Wilson, I.H. Rosenberg, and J. Selhub. Low circulation vitamin Bgis associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation 103 2788—2791 (2001). 

Diet and nutrition have been extensively investigated as risk factors for CHD. Many dietary factors have been linked directly to an increased or decreased risk of CHD or to major established risk factors of CHD like high blood pressure, disordered blood fats (dyslipidemia), diabetes and metabolic syndrome, overweight and obesity, and also to emerging risk factors like inflammatory markers and homocysteine. Nutrition influences atherogen-esis, thrombosis, and inflammation - all of which are interconnected pathways that lead to CHD. 

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