Due to a lack of enzymes that are necessary for the proper metabolism of vitamin B12, patients with MS have elevated levels of an amino acid called "homocysteine". I posted a great deal on its involvement in the MS disease process on this thread. general-discussion-f1/topic22806.html
Homocysteine activates MMP-9. Here is the conclusion from the following study: "These data suggest that Hcy increases microvascular permeability, in part, through MMP-9 activation."
Am J Physiol Heart Circ Physiol. 2006 Mar;290(3):H1206-13. Epub 2005 Oct 28.
Homocysteine causes cerebrovascular leakage in mice.
Lominadze D, Roberts AM, Tyagi N, Moshal KS, Tyagi SC.
"Elevated plasma homocysteine (Hcy) is associated with cerebrovascular disease and activates matrix metalloproteinases (MMPs), which lead to vascular remodeling that could disrupt the blood-brain barrier. To determine whether Hcy administration can increase brain microvascular leakage secondary to activation of MMPs, we examined pial venules by intravital video microscopy through a craniotomy in anesthetized mice. Bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC) was injected into a carotid artery to measure extravenular leakage. Hcy (30 microM/total blood volume) was injected 10 min after FITC-BSA injection. Four groups of mice were examined: 1) wild type (WT) given vehicle; 2) WT given Hcy (WT + Hcy); 3) MMP-9 gene knockout given Hcy (MMP-9-/- + Hcy); and 4) MMP-9-/- with topical application of histamine (10(-4) M) (MMP-9-/- + histamine). In the WT + Hcy mice, leakage of FITC-BSA from pial venules was significantly (P < 0.05) greater than in the other groups. There was no significant leakage of pial microvessels in MMP-9-/- + Hcy mice. Increased cerebrovascular leakage in the MMP-9-/- + histamine group showed that microvascular permeability could still increase by a mechanism independent of MMP-9. Treatment of cultured mouse microvascular endothelial cells with 30 microM Hcy resulted in significantly greater F-actin formation than in control cells without Hcy. Treatment with a broad-range MMP inhibitor (GM-6001; 1 microM) ameliorated Hcy-induced F-actin formation. These data suggest that Hcy increases microvascular permeability, in part, through MMP-9 activation."
Research confirms that homocysteine is elevated in patients with diabetes and that it interferes with normal wound healing. Here is an excerpt from my book on this.
"By interfering with nitric oxide (NO), homocysteine can prevent wounds from healing normally. The study entitled “Homocysteine--a stealth mediator of impaired wound healing: a preliminary study” states, “Ongoing experimental and clinical wound healing studies have now clearly established NO as a critical mediator of normal tissue repair. Angiogenesis, granulation tissue formation, epidermal migration, collagen deposition, and microvascular homeostasis are significant vulnerary processes, critical to normal wound repair, that are regulated by NO production and bioactivity…Homocysteine antagonizes NO production via multiple pathways…”(Boykin, 2006)."
Here is some information on the involvement of homocysteine in diabetes.
In the following study published in the Annals of Internal Medicine the researchers concluded that homocysteine was a strong and independent risk factor for coronary heart disease (CHD) events in patients with type 2 diabetes. Approximately 80% of people with diabetes die of cardiovascular disease.
Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus.
Soinio, M., J. Marniemi, M. Laakso, S. Lehto, T. Rönnemaa. 2004. Ann Intern Med. 140(2):94-100.
“…In this large cohort of patients with type 2 diabetes, plasma homo cysteine level was a strong and independent risk factor for CHD events.”
In the following study of 65 patients with type 2 diabetes, elevated levels of homocysteine were found to be independently associated with the prevalence of peripheral neuropathy. The authors suggested that this association could be explained either by direct cytotoxic effects on nerve function, or by small vessel occlusions caused by endothelial damage. This results in a loss of blood supply to nerve fibers, a pathogenetic mechanism of peripheral neuropathy.
Relation between homocysteinaemia and diabetic neuropathy in patients with type 2 diabetes mellitus.
Ambrosch, A., J. Dierkes, R. Lobmann, W. Kühne, W. König, C. Luley, H. Lehnert. 2001. Diabet Med. 18(3):185-92.
“…Since homocysteine exhibits toxic effects on vascular endothelial cells, the association between homocysteine and the prevalence of neuropathy in type 2 diabetes mellitus was investigated… homocysteine levels…and the frequency of hyperhomocysteinemia were significantly increased in neuropathic patients… The data indicate that homocysteine is independently associated with the prevalence of diabetic neuropathy in a collective of type 2 diabetic patients.”
Homocysteine is also associated with ulceration in type 2 diabetes. The study entitled “Plasma homocysteine levels are associated with ulceration of the foot in patients with type 2 diabetes” concluded that for each micromol increase in plasma homocysteine levels there was a 10% increase in the risk of diabetic foot ulceration (González, 2010).