Protein kinase C in enhanced vascular tone in diabetes mellitus

Kizub, Igor V.; Klymenko, Kateryna I.; Soloviev, Anatoly I.

doi:10.1016/j.ijcard.2014.04.117

Cited by 75 publications

(72 citation statements)

References 210 publications

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“…These results indicate that basal overcontraction of the diabetic ILA under NG conditions is caused by overactivation of calcium-independent PKC (Scheme 1), which might be caused by diabetic hyperglycemia in vivo. Overactivation of PKC in diabetes was also reported in the rat renal artery (Noh and King, 2007;Kizub et al, 2014). This report showed that the expression of calcium-dependent PKC activity is enhanced in diabetes and is associated with attenuated coronary artery vasodilation, without affecting voltage-gated calcium channel activity.…”

Section: Discussionsupporting

confidence: 56%

Two Types of Overcontraction Are Involved in Intrarenal Artery Dysfunction in Type II Diabetic Mouse

Nobe

Takenouchi

Kasono

et al. 2014

J Pharmacol Exp Ther

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Contractile responses in small intrarenal arteries are associated with diabetic nephropathy. However, the mechanisms that induce and maintain altered small vessel contraction are not clearly understood. To further understand intrarenal artery dysfunction in diabetes, phenylephrine (PE)-induced force development was assessed in the intrarenal artery [interlobar artery (ILA)] in control (lean) and type II diabetic (ob/ob) mice. PE-induced dosedependent force development in the ILA was significantly greater in ob/ob mice than in lean mice (592.8 6 5.2 and 770.1 6 12.1 m/mm tissue, respectively, following administration of 30 mM PE, n 5 5). Under high-glucose conditions (twice the normal concentration of glucose), PE-induced force development in the ILA was only enhanced in ob/ob mice (946.0 6 18.2 mN/mm tissue; n 5 5). ILA dysfunction reduces blood flow to the glomerulus and may induce diabetic nephropathy. Basal overcontraction of the ILA in ob/ob mice under normal-glucose conditions was reduced by pretreatment with rottlerin, a calcium-independent protein kinase C (PKCd) inhibitor. Total PKC activity was also reduced by rottlerin. Under high-glucose conditions, the enhanced ILA contraction in diabetic mice was suppressed by rho A and rho kinase inhibitors. Our results indicate two types of ILA dysfunction in diabetes, as follows: 1) a basal increase in PE-induced contraction under normal-glucose conditions, and 2) extracellular glucose-dependent enhancement of PE-induced contraction. We believe that these dysfunctions are mediated by the activation of the PKCd and rho A-rho kinase pathways, respectively.

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Section: Discussionsupporting

confidence: 56%

Two Types of Overcontraction Are Involved in Intrarenal Artery Dysfunction in Type II Diabetic Mouse

Nobe

Takenouchi

Kasono

et al. 2014

J Pharmacol Exp Ther

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“…Diabetic vascular disease is the leading cause of death and disability in diabetic patients; 30-40% of the patients are subject to at least one vascular complications after 10 years (Tavintharan et al, 2014). Numerous studies have shown the association of diabetes mellitus vascular complications with oxidative stress in endothelial cells and endothelial cells derived from progenitor cells (mainly in the bone marrow) (Kizub et al, 2014;Prieto et al, 2014;Yiu and Tse, 2014). Conventionally, high blood sugar is believed to lead to microvascular and macrovascular disease via four pathways: 1) polyol signaling pathway imbalances, 2) increase in advanced glycation end-product (AGE) formation, 3) increased activation of protein kinase C; and 4) imbalances in the hexosamine signaling pathway (van den Oever et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Effect of procyanidine on VEGFR-2 expression and transduction pathway in rat endothelial progenitor cells under high glucose conditions

Y¹,

Wj²,

Zhu³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The protective effect of procyanidine and its oligomers against high glucose-mediated oxidative stress injury in endothelial progenitor cells (EPCs), and effect of procyanidin on vascular endothelial growth factor receptor-2 (VEGFR-2) expression and downstream signal pathway were analyzed in vitro. Rat bone marrow mononuclear cells were isolated, cultured under normal and high glucose (HG) conditions, and the changes in cell morphology observed. The EPCs were identified, and the oxidative stress products produced by EPCs (under normal and HG conditions) were quantified. Subsequently, an appropriate number of EPCs were cultured with and without procyanidin (OPC), and the MDA concentration and relative expression of VEGFR-2, AKT, IkB-a, and nuclear factor (NF)-kB were detected 1, 3, 5, and 7 days post-culture. We observed minor (round, translucent, gradually adhering) and significant (fusiform morphology/ pebble distribution) cell morphological changes 3 and 7 days post-culture, respectively. Apoptosis and oxidative stress product release in EPCs cultured with HG increased significantly compared to the control group (P < 0.05). The oxidative stress product generation and relative expression of VEGFR-2, AKT, IkB-a, and NF-kB were not significantly affected by OPC addition in normal glucose conditions (P > 0.05); alternately, products generated as a result of oxidative stress were significantly reduced, the relative expression of VEGFR-2, AKT, and NF-kB protein was upregulated, and that of IkB-a was downregulated (P < 0.05) in HG + OPC EPCs. Therefore, procyanidin may promote cell proliferation by alleviating oxidative damage to EPCs under HG conditions, and upregulating VEGFR-2 expression and its downstream signal pathway.

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“…Of these, cardiovascular disorders, end-stage renal disease, and blindness are of particular concern (3). Both type 1 and type 2 diabetes may be accompanied with circulatory anomalies that account for up to 80% of premature mortality and a heavy health care burden (3). Macrovascular circulatory abnormalities include angiopathy, atherosclerosis, increased vascular tone, arterial hypertension, and calcification in both medium and large arteries.…”

mentioning

confidence: 99%

“…Macrovascular circulatory abnormalities include angiopathy, atherosclerosis, increased vascular tone, arterial hypertension, and calcification in both medium and large arteries. Microvascular complications include retinopathy, nephropathy, and peripheral neuropathy (3,4). Regardless of the affected site, vascular injury shares some common histopathological features of endothelial and smooth muscle dysfunction.…”

mentioning

confidence: 99%

“…A plethora of theories have been postulated for diabetic vascular injury. They include increased flux through polyol and hexosamine pathways, activation of protein kinase C (PKC), oxidative stress, and accumulation of advanced glycation end products that lead to abnormal blood flow, apoptosis, hyperpermeability, and accumulation of extracellular matrix (3,5). Therapeutic strategies to address diabetic vascular injury include removing risk factors, such as hyperinsulinemia, hypertension, obesity, and hyperglycemia; blocking injurious mechanisms; and promoting protective processes, such as insulin-regulated genes, antioxidant or anti-inflammatory factors, or cell survival factors (5).…”

mentioning

confidence: 99%

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