Reducing the burden of diabetes: managing cardiovascular disease

Keen, H; Clark, Charles M.; Laakso, Markku

doi:10.1002/(sici)1520-7560(199905/06)15:3<186::aid-dmrr30>3.3.co;2-x

Cited by 4 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, exposure of endothelial cells to high glucose leads to augmented production of superoxide anion, which may quench nitric oxide, thereby reducing the efficacy of a potent endothelium-derived vasodilator system that participates in the general homeostasis of the vasculature. Further, the reaction of superoxide and NO not only diminishes the activity of a beneficial vasodilatory pathway but also generates a toxic oxidant species, peroxynitrite (see below) [1,2,3,4,5]. In further support of the consequential injurious role of oxidative stress, many of the adverse effects of high glucose on endothelial functions, such as reduced endothelial-dependent relaxation and delayed cell replication, are reversed by antioxidants [15,16].…”

Section: Oxyradicalsmentioning

confidence: 99%

“…The precise physiological roles of PARP remain undefined; its traditional role as a DNA-repair enzyme has been questioned [2]. PARP appears to play diverse roles, participating in DNA repair [3,4], chromatin relaxation [5], cell differentiation [6], DNA replication [7], transcriptional regulation [8], control of cell cycle [9], p53 expression and apoptosis [10], and transformation [11].…”

Section: Peroxynitritementioning

confidence: 99%

“…Many of these approaches (such as the aldose reductase pathway, the protein kinase C pathway, the advanced glycation end product pathway, the angiotensin-converting enzyme related endothelial dysfunction and the folate pathway) are closely related to free-radical or oxidant-related processes (as reviewed in [1,2,3,4,5]). As PARP occupies a critical position in a self-amplifying cycle of oxidant-driven damage, it is appropriate then to ask whether PARP inhibition is a candidate for clinical treatment of diabetic vascular dysfunction.…”

Section: Summary and Implications: Role Of Parp Activation In Diabetimentioning

confidence: 99%

“…The processes involved in atherothrombotic disease are complex and include variation in lipid metabolism, vascular responses, cell/cell interactions, and the fluid and cellular phases of coagulation and fibrinolysis. The complex interactions between these processes are crucially altered by the metabolic milieu that characterizes diabetes mellitus, tipping the delicate balance towards atheroma formation, platelet aggregation and thrombus formation [1,2,3,4,5].…”

mentioning

confidence: 99%

See 3 more Smart Citations

Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation

2001

View full text Add to dashboard Cite

Peroxynitrite and hydroxyl radicals are potent initiators of DNA single-strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP ribose) polymerase (PARP). In response to high glucose incubation medium in vitro, or diabetes and hyperglycemia in vivo, reactive nitrogen and oxygen species generation occurs. These reactive species trigger DNA single-strand breakage, which induces rapid activation of PARP. PARP in turn depletes the intracellular concentration of its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation. This process results in acute endothelial dysfunction in diabetic blood vessels. Accordingly, inhibitors of PARP protect against endothelial injury under these conditions. In addition to the direct cytotoxic pathway regulated by DNA injury and PARP activation, PARP also appears to modulate the course of inflammation by regulating the activation of nuclear factor kappaB, and the expression of a number of genes, including the gene for intercellular adhesion molecule 1 and the inducible nitric oxide synthase. The research into the role of PARP in diabetic vascular injury is now supported by novel tools, such as new classes of potent inhibitors of PARP and genetically engineered animals lacking the gene for PARP. Pharmacological inhibition of PARP emerges as a potential approach for the experimental therapy of diabetic vascular dysfunction.

show abstract

Section: Oxyradicalsmentioning

confidence: 99%

Section: Peroxynitritementioning

confidence: 99%

Section: Summary and Implications: Role Of Parp Activation In Diabetimentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation

2001

View full text Add to dashboard Cite

show abstract

“…Diabetic subjects have been shown to have high risk for CVD compared to non-diabetic population [2]. Atherosclerosis, a process which is exacerbated during diabetes, leads to the development of CVD.…”

Section: Introductionmentioning

confidence: 99%

Salutary Effect of Cassia auriculata L. Leaves on Hyperglycemia-Induced Atherosclerotic Environment in Streptozotocin Rats

et al. 2011

View full text Add to dashboard Cite

Diabetes mellitus is very often associated with dyslipidemia, increased oxidative stress and endothelial dysfunction that could develop atherosclerosis and consequently cardiovascular diseases. Medicinal plants with reputed traditional use to treat diabetes and cardiovascular diseases might provide valuable drugs. Therefore, the present study was designed to evaluate anti-atherosclerotic potential of aqueous extract of Cassia auriculata L. leaves in streptozotocin (STZ)-induced diabetic rats. The rats were rendered diabetic by STZ (45 mg/kg, ip). Diabetic rats were orally administered C. auriculata leaf extract at 400 mg/kg dose daily for 21 days. The supplementation of extract to the diabetic rats produced significant reduction in fasting blood glucose along with significant reversal in altered serum lipid profile and apolipoprotein B. Lipid peroxidation was found to be significantly suppressed in extract-fed diabetic rats. The significant reduction in serum levels of oxidized low-density lipoprotein, soluble vascular cell adhesion molecule and plasma fibrinogen with a concomitant elevation in serum nitric oxide was observed in diabetic rats following treatment with extract. Histopathological examination of heart myocardium of extract-treated diabetic rats revealed reversal of fatty change toward normal. These results suggest that C. auriculata aqueous leaf extract exhibits anti-atherosclerotic role in the diabetic state and it indicates toward the notion that extract may help to prevent the progression of cardiovascular diseases.

show abstract