Reduced thrombosis in Klkb1−/− mice is mediated by increased Mas receptor, prostacyclin, Sirt1, and KLF4 and decreased tissue factor

Stavrou, Evi X.; Fang, Chao; Merkulova, Alona; Alhalabi, Omar; Grobe, Nadja; Antoniak, Silvio; Mackman, Nigel; Schmaier, Alvin H.

doi:10.1182/blood-2014-01-550285

Cited by 80 publications

(108 citation statements)

References 46 publications

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“…[58][59][60] Klkb1 2/2 mice died on intravenous pure polyP infusion. 56 The animals were not protected from prostasome challenge either (Figure 1), supporting the presence of polyP on prostasomes. Infusion of polyP into Bdkrb2 2/2 animals induced lethal PE, 15 and consistently, the mice were also susceptible to prostasome-triggered PE.…”

Section: Discussionmentioning

confidence: 79%

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The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

Nickel

Ronquist

Länger

et al. 2015

Blood

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Section: Discussionmentioning

confidence: 79%

“…55 PolyP/FXII inhibition and deficiency in factors XI, XII, or HK interfered with prostasome-induced lethal PE (Figure 1). Similar to infusion of pure polyP 56 and platelet stimulation, 57 injection of prostasomes induced microvascular PE. In humans, microvascular PE represents a complication of tumor cell embolism.…”

Section: Discussionmentioning

confidence: 85%

The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

Nickel

Ronquist

Länger

et al. 2015

Blood

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126

111

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“…Additionally, plasma PK has a role in vascular remodeling by promoting growth of vascular smooth muscle cells through transactivation of epidermal growth factor receptors (10). Finally, Klkb1 −/− mice (PK deficient) have delayed arterial thrombosis by increasing protective vascular transcription factors Sirt1 and Kruppel-like factor 4 to reduce vessel wall tissue factor and inflammation, a forerunner of vessel atherothrombosis (11). …”

Section: Introductionmentioning

confidence: 99%

Plasma Prekallikrein Is Associated With Carotid Intima-Media Thickness in Type 1 Diabetes

et al. 2015

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The hypothesis that plasma prekallikrein (PK) is a risk factor for the development of vascular complications was assessed in a study using the Diabetes Control and Complications Trial (DCCT)/Epidemiology and Diabetes Interventions and Complications (EDIC) cohort of subjects with type 1 diabetes. The circulating levels of plasma PK activity were measured in the plasma of 636 subjects with type 1 diabetes (EDIC years 3–5). Common and internal carotid intima-media thickness (IMT) were measured by B-mode ultrasonography in EDIC years 1 and 6. Plasma PK levels were positively and significantly associated with BMI, hemoglobin A1c, systolic blood pressure, total cholesterol, LDL cholesterol, and triglycerides but not with age, sex, duration of diabetes, or HDL cholesterol. Univariate and multivariable statistical models after controlling for other risk factors consistently demonstrated a positive association between plasma PK and progression of internal carotid IMT. Multivariate analysis using a general linear model showed plasma PK to be significantly associated with progression of both internal and combined IMT (Wilks Λ P value of 0.005). In addition, the mean internal carotid IMT levels were higher in subjects with plasma PK levels in the highest 10th percentile compared with subjects with plasma PK levels in the lower 10th percentile (P = 0.048). These novel findings implicate plasma PK as a risk factor for vascular disease in type 1 diabetes.

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“…200 As expected, these mice also have reduced bradykinin levels, which results in downregulation of bradykinin receptor 2, a major negative regulator of PGI 2 . With reduced bradykinin receptor 2, the increased PGI 2 , in turn, upregulates transcription factors Sirt1 and KLF4, leading to suppression of TF and enhanced expression of TM, 201 thereby preventing thrombosis. Similarly, mice lacking bradykinin receptor 2 are protected against thrombosis.…”

Section: Contact Activation and Kallikrein-kininmentioning

confidence: 99%

Cross Talk Pathways Between Coagulation and Inflammation

Foley

Conway

2016

Circulation Research

464

414

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Anatomic pathology studies performed over 150 years ago revealed that excessive activation of coagulation occurs in the setting of inflammation. However, it has taken over a century since these seminal observations were made to delineate the molecular mechanisms by which these systems interact and the extent to which they participate in the pathogenesis of multiple diseases. There is, in fact, extensive cross talk between coagulation and inflammation, whereby activation of one system may amplify activation of the other, a situation that, if unopposed, may result in tissue damage or even multiorgan failure. Characterizing the common triggers and pathways are key for the strategic design of effective therapeutic interventions. In this review, we highlight some of the key molecular interactions, some of which are already showing promise as therapeutic targets for inflammatory and thrombotic disorders. (Circ Res.

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Reduced thrombosis in Klkb1−/− mice is mediated by increased Mas receptor, prostacyclin, Sirt1, and KLF4 and decreased tissue factor

Abstract: Key Points The reduced thrombosis in Klkb1−/− mice is not by defective contact activation. Overexpressed renal Mas with elevated plasma prostacyclin increases aortic Sirt1 and KLF4 and reduces aortic TF protecting Klkb1−/− mice.

Cited by 80 publications

References 46 publications

The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

Plasma Prekallikrein Is Associated With Carotid Intima-Media Thickness in Type 1 Diabetes

Cross Talk Pathways Between Coagulation and Inflammation

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