PKCδ Impaired Vessel Formation and Angiogenic Factor Expression in Diabetic Ischemic Limbs

Lizotte, Farah; Paré, Martin; Denhez, Benoît; Leitges, Michael; Guay, Andréanne; Geraldes, Pedro

doi:10.2337/db12-1432

Cited by 35 publications

(54 citation statements)

References 49 publications

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“…Excessive angiogenesis exists in diabetic retinopathy and impaired angiogenesis in coronary and peripheral circulations. 1,10,19,26 In our study, there was more frequent collateral formation in the diabetes group. Greater extent of collaterals (more than one-third of the MCA distribution) was also detected in patients with T2DM.…”

Section: Surgical Treatmentmentioning

confidence: 64%

“…4,8,13 Different outcomes of neovascularization attributed to DM have been found in various organ systems. 1,10,19,26 The effect of DM on cerebral neovascularization remains unclear. In this study, we sought to investigate the effect of EDAS on clinical outcomes and explore the distinction of collateral circulation between MMD patients with and without type 2 diabetes mellitus (T2DM).…”

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confidence: 99%

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Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes

Ren

Zhang

Liu

et al. 2016

JNS

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M oyaMoya disease (MMD), a cerebral vascular disease, is characterized by progressive stenosis and occlusion of the terminal portion of the bilateral internal carotid arteries, leading to the formation of an abnormal vascular network composed of collateral pathways at the base of the brain. MMD can cause a reduction in the blood supply to the brain, and there are 2 major etiological categories of symptoms: those due to brain ischemia (i.e., stroke, transient ischemic attack, and seizure) and those due to the deleterious consequences of the compensatory mechanisms in response to ischemia (i.e., hemorrhage from fragile collateral vessels and headache aBBreViatiONS CBF = cerebral blood flow; DM = diabetes mellitus; EDAS = encephaloduroarteriosynangiosis; MCA = middle cerebral artery; MMD = moyamoya disease; mRS = modified Rankin Scale; PCA = posterior cerebral artery; STA = superficial temporal artery; T2DM = Type 2 DM. SuBmitted January 29, 2015. OBJectiVe Debate exists regarding the merits and shortcomings of an indirect bypass procedure for treating adult patients with moyamoya disease (MMD). Considerable variation in neovascularization occurs among different organs in patients with diabetes mellitus. Here, the effect of encephaloduroarteriosynangiosis on MMD associated with Type 2 diabetes mellitus (T2DM) is evaluated. methOdS A retrospective and 1:2 matched case-control study was conducted in moyamoya patients with or without T2DM (n = 180). Postoperative collateral formations were graded according to the Modified Collateral Grading System that originated from the Matsushima Angiographic Stage Classification. Neurological function outcomes before and after the operation were evaluated according to the modified Rankin Scale. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. reSultS There was no statistically significant difference in the constituent ratios of initial symptom and preoperative Suzuki stage between patients with and without T2DM. Progression of angiopathy around the circle of Willis was postoperatively observed in bilateral internal carotid arteries in both groups. Patients with T2DM had a higher postoperative Suzuki stage (p < 0.01) and more frequent development of collateral angiogenesis germinating from the external carotid after indirect revascularization procedures in the surgical cerebral hemisphere (82.7% vs 72.2%; p < 0.05). The extent of postoperative collateral formation in patients with diabetes mellitus was significantly higher (p < 0.01). Postoperative clinical improvement in the diabetes group was more common after revascularization procedures (p < 0.05), and the diabetes group had lower modified Rankin Scale scores (p < 0.05) in comparison with the nondiabetes group. Late postoperative stroke and posterior cerebral artery involvement were identified as predictors of unfavorable clinical outcome in both groups, while T2DM was associated with a favorable clinical outcome. cONcluSiONS Encephaloduroarteriosynangio...

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Section: Surgical Treatmentmentioning

confidence: 64%

mentioning

confidence: 99%

Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes

Ren

Zhang

Liu

et al. 2016

JNS

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“…As a consequence, PKCδ-deficient diabetic mice show significantly increased blood flow, capillary density, and number of capillaries. 30 Finally, angiopoietins and their receptor Tie-2 have been shown to harmonize vascular regeneration in diabetic tissue. Tie-2 expression is significantly reduced, whereas angiopoietin 2 (Ang-2) is increased in Leprdb/Leprdb mice subjected to MI.…”

Section: Additional Angiogenic-related Pathwaysmentioning

confidence: 99%

Diabetes Mellitus and Ischemic Diseases

Howangyin

Silvestre

2014

ATVB

124

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Hypoxia-Inducible Factor 1Hypoxia, at least in part through activation of the hypoxiainducible factor 1 (HIF-1) α-related pathways, controls all steps of the postischemic revascularization process. Recent studies uncover that destabilization of HIF-1 is most likely the event that transduces hyperglycemia into the loss of the cellular response to hypoxia in most diabetic complications.2 Levels of HIF-1α are decreased in biopsies from foot ulcers of patients with diabetes mellitus as compared with venous ulcers that share the same hypoxic environment but are not exposed to hyperglycemia.3 Downregulation of HIF-1 in response to hyperglycemia also seems to account for the decreased collateral growth triggered by myocardial ischemia in patients with © 2014 American Heart Association, Inc. Abstract-In patients with diabetes mellitus, the ability of ischemic tissue to synchronize the molecular and cellular events leading to restoration of tissue perfusion in response to the atherosclerotic occlusion of a patent artery is markedly impaired. As a consequence, adverse tissue remodeling and the extent of ischemic injury are intensified, leading to increased morbidity and mortality. Growing evidence from preclinical and clinical studies has implicated alterations in hypoxia-inducible factor 1 levels in the abrogation of proangiogenic pathways, including vascular endothelial growth factor A/phosphoinositide 3′ kinase/AKT/endothelial nitric oxide synthase and in the activation of antiangiogenic signals characterized by accumulation of advanced glycation end products, reactive oxygen species overproduction, and endoplasmic reticulum stress. In addition, the diabetic milieu shows a switch toward proinflammatory antiregenerative pathways. Finally, the mobilization, subsequent recruitment, and the proangiogenic potential of the different subsets of angiogenesis-promoting bone marrow-derived cells are markedly impaired in the diabetic environment. In this review, we will give an overview of the current understanding on the signaling molecules contributing to the diabetes mellitusinduced impairment of postischemic revascularization mainly in the setting of myocardial infarction or critical limb ischemia. (Arterioscler Thromb Vasc Biol. 2014;34:1126-1135.)

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“…PRKCD is the only protein among the 5 candidate targets of PQS that is known to block angiogenesis [24]. Western blot analysis showed increased expression of PRKCD in ischemic myocardium (vs. sham surgery ; Fig.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

“…PRKCD, known as PKCδ in porcine species, belongs to the PKC family and is expressed in endothelial cells (ECs) and smooth muscle cells (SMCs) [32,33]. A study in rats demonstrated that PKCδ could impair vessel formation in diabetic ischemic limbs [24], suggesting that PKCδ is a negative regulator of angiogenesis. In our study, we showed PQS could reverse CMI-induced elevation in PRKCD expression, indicating that PQS may promote angiogenesis through blocking the expression of PRKCD.…”

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confidence: 99%

Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic Ischemia

Guo

Liu

Guo

et al. 2018

Cell Physiol Biochem

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Background/Aims: Previous studies in rat models of myocardial ischemia showed that Panax quinquefolium saponins (PQS) could attenuate ischemic/reperfusion injury, increase vessel density and improve cardiac function. In the current study, we examined whether PQS could attenuate myocardial dysfunction in a swine model of chronic myocardial ischemia (CMI). Methods: CMI was established in Bama mini-pigs by placing amroid constrictor on the left anterior descending artery (LAD). Starting from 2 months after the surgery, pigs randomly received PQS (30 mg/kg/day), atorvastatin (1.5 mg/kg/day), or no drug for one month (n=6). A group of pigs receiving sham surgery was included as an additional control. Glucose utilization was assessed with positron emission tomography-computer tomography (PET-CT). Cardiac function was assessed with echocardiography. Myocyte size, nuclear density, and arteriolar density were examined in tissue section obtained from the ischemia area. Potential molecular targets of PQS were identified using proteomic analysis with isobaric tags for relative and absolute quantitation (iTARQ) and network pharmacology. Results: In comparison to the sham controls, pigs implanted with ameroid constrictor had decreased ventricular wall motion, left ventricular ejection fraction (LVEF), and glucose utilization. PQS significantly increased cardiac function and glucose utilization. Arteriole density and myocyte nuclear density were increased. Myocyte diameter was decreased. PQS also attenuated the CMI-induced change of protein expression profile. The effects of atorvastatin were generally similar to that of PQS. However, PQS attenuated the reduction of left ventricular systolic WT induced by CMI more robustly than atorvastatin. Conclusion: The results from the current study supports the use of PQS in patients with coronary artery disease.

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PKCδ Impaired Vessel Formation and Angiogenic Factor Expression in Diabetic Ischemic Limbs

Cited by 35 publications

References 49 publications

Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes

Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes

Diabetes Mellitus and Ischemic Diseases

Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic Ischemia

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