Omega-3E treatment regulates matrix metalloproteinases and prevents vascular reactivity alterations in diabetic rat aortaThis article is one of a selection of papers published in a special issue on Advances in Cardiovascular Research.

Abstract

It is known that increased generation of oxidants and (or) reduced endogenous antioxidant defense mechanisms are associated with the etiology of diabetic vascular complications. Although a close correlation exists between increased oxidative stress and the activation of matrix metalloproteinases (MMPs), little is known about the effect of hyperglycemia on the regulation and contribution of MMPs in the vascular system. Therefore, we aimed to examine whether omega-3E (50 mg/kg per day for 4 weeks), a long-chain (n-3) polyunsaturated fatty acid enriched with vitamin E, has a beneficial effect on vascular dysfunction via affecting MMPs in streptozotocin-diabetic rat aorta. Omega-3E treatment improved the diabetes-induced impairment of phenylephrine-induced contraction and isoproterenol-induced relaxation responses of aorta. It also exhibited marked protection against diabetes-induced degenerative changes in smooth muscle cell morphology. Biochemical data showed that this treatment significantly prevented important changes, such as inhibition of MMP-2 and MMP-9 activity, loss of tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) protein, increase in tissue levels of thiol oxidation, endothelin-1, protein kinase C (PKC), and cAMP production, and decrease in tissue level of nitrite. These results indicated that omega-3E significantly improved impaired vascular responses and regulated the activity of MMPs via preventing oxidative injury. Overall, the data suggest that omega-3E ameliorates or prevents vascular reactivity alterations in diabetes. Such an observation provides preliminary evidence for omega-3E's potential as a therapeutic agent for the prevention of vascular disorders in diabetes.

Role of ROCK upregulation in endothelial and smooth muscle vascular functions in diabetic rat aorta

“…As illustrated in Figure 1F, the maximal responses to Phe-precontraction in the either diabetic group or control group in the presence of L-NAME are not significantly different from those of absence of L-NAME. Our first data with diabetics can provide a first information related with diabetes-induced a contractile vascular function, of which showed, that contractions in response to phenylephrine were not effected from NO-release in diabetic rat aortic rings [14,15,18]. …”

“…Although many studies were performed with several animal models, there are conflicts related with the vascular responses to contractile agents in the diabetic subjects. Accordingly, some studies suggested increased sensitivity to noradrenaline [28], whereas other studies, including our team’s studies, reported an attenuated contractile response to noradrenaline in the aortas from diabetic animals [14,15,18,29]. These studies mainly stated that the impaired contractile responses to phenylephrine applications could be due to a change in α-adrenergic receptor expression in the vasculature [30].…”

“…Aortic rings were prepared as described previously [15]. The rings were set at 1-g passive tension and allowed to equilibrate for 60 min, and then first their contractile ability was assessed by exposure to 60 mM KCl.…”

Matrix Metalloproteinase-1 and -9 in Human Placenta during Spontaneous Vaginal Delivery and Caesarean Sectioning in Preterm Pregnancy

“…The activity of MMPs like MMP-2, -3, and -9 are reported to be regulated by long chain polyunsaturated fatty acids (LCPUFA) [17]–[19]. Our earlier studies in preterm deliveries indicate increased oxidative stress and reduced LCPUFA especially docosahexaenoic acid (DHA) levels in preterm pregnancy [20], [21].…”

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

“…We have recently reported increased placental levels of MMP1 (collagenase) and MMP9 (gelatinase) in women delivering preterm (Sundrani et al 2012). The activity of MMPs is reported to be regulated by homocysteine, oxidative stress, and long-chain polyunsaturated fatty acids (LCPUFA; Guo et al 2006, Kundu et al 2009, Solakivi et al 2009, Zainal et al 2009, Zeydanli & Turan 2009, Ke et al 2010.…”