Vascular Toxicity of Tyrosine Kinase Inhibitors: Coronary Artery Disease

2021 ◽  
pp. 55-56
Author(s):  
Wendy Schaffer
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Vascular Toxicity ◽  
Artery Disease

Prognostic use of soluble fms-like tyrosine kinase-1 and placental growth factor in patients with coronary artery disease

2016 ◽  
Vol 10 (1) ◽  
pp. 95-106 ◽  
Author(s):  
Christoph Sinning ◽  
Renate B Schnabel ◽  
Tanja Zeller ◽  
Moritz Seiffert ◽  
Hans J Rupprecht ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Placental Growth Factor ◽  
Artery Disease

scholarly journals A phosphoproteomic signature in endothelial cells predicts vascular toxicity of tyrosine kinase inhibitors used in CML

2018 ◽  
Vol 2 (14) ◽  
pp. 1680-1684 ◽  
Author(s):  
Srila Gopal ◽  
Qing Lu ◽  
Joshua J. Man ◽  
Wendy Baur ◽  
Sitara P. Rao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Drug Development ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Screening Tool ◽  
Kinase Inhibitors ◽  
Vascular Toxicity ◽  
Key Points

Key Points Newer CML kinase inhibitors increase ischemia risk and are toxic to endothelial cells where they produce a proteomic toxicity signature. This phosphoproteomic EC toxicity signature predicts bosutinib to be safe, providing a potential screening tool for safer drug development.

Effects of coronary artery disease on expression and microvascular response to VEGF

1998 ◽  
Vol 275 (4) ◽  
pp. H1411-H1418 ◽  
Author(s):  
Caroline Métais ◽  
Jianyi Li ◽  
Jian Li ◽  
Michael Simons ◽  
Frank W. Sellke
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Growth Factor ◽  
Nitric Oxide Synthase ◽  
Substance P ◽  
Tyrosine Kinase ◽  
Northern Analysis ◽  
Artery Disease ◽  
Oxide Synthase

The effects of coronary artery disease (CAD) on human coronary microvascular responses to vascular endothelial growth factor (VEGF) and the alterations of the myocardial expressions of VEGF and its flk-1 and flt-1 receptors were examined in 48 patients. Microvascular studies were performed in vitro with video microscopy. The expressions of VEGF and its receptors were examined using Northern analysis of total mRNA, and the expressions of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were examined by RT-PCR. VEGF and hepatocyte growth factor (HGF) caused potent relaxations of microvessels. These responses were reduced in the presence of N G-nitro-l-arginine and the tyrosine kinase inhibitor genistein or in microvessels from patients with CAD. Relaxations to substance P and sodium nitroprusside were similar in both groups. The substance P response was abolished in the presence of N G-nitro-l-arginine. The expression of VEGF and its receptors and the expression of cNOS and iNOS were not altered in patients with CAD. In conclusion, VEGF and HGF elicit the release of nitric oxide through activation of tyrosine kinase receptors. CAD is associated with reduced vascular responses to both VEGF and HGF; this is not likely due to a reduced expression of VEGF or flt-1 or flk-1 receptors and not due to a generalized endothelium dysfunction despite the presence of mild hypercholesterolemia in these patients with CAD. These findings may have important implications regarding the efficacy of endogenous and exogenous VEGF in patients with risk factor for CAD.

scholarly journals Neutrophil Extracellular Traps Are Increased in Chronic Myeloid Leukemia and Are Differentially Affected by Tyrosine Kinase Inhibitors

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 119
Author(s):  
Alona Telerman ◽  
Galit Granot ◽  
Chiya Leibovitch ◽  
Osnat Yarchovsky-Dolberg ◽  
Adi Shacham-Abulafia ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Cardiovascular Complications ◽  
Arginine Deiminase ◽  
Neutrophil Extracellular Trap ◽  
Vascular Toxicity

Cardiovascular complications are increasingly reported with the use of certain tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML). We studied neutrophil extracellular trap (NET) formation in CML and evaluated the effect of TKIs on NET formation. Neutrophils isolated from treatment-naïve patients with CML showed a significant increase in NET formation compared to matched controls at baseline and after stimulation with ionomycin (IO) and phorbol 12-myristate 13-acetate (PMA). Expression of citrullinated histone H3 (H3cit), peptidyl arginine deiminase 4 (PAD4) and reactive oxygen species (ROS) was significantly higher in CML samples compared to controls. Pre-treatment of neutrophils with TKIs was associated with a differential effect on NET formation, and ponatinib significantly augmented NET-associated elastase and ROS levels as compared to controls and other TKIs. BCR-ABL1 retroviral transduced HoxB8-immortalized mouse hematopoietic progenitors, which differentiate into neutrophils in-vitro, demonstrated increased H3cit & myeloperoxidase (MPO) expression consistent with excess NET formation. This was inhibited by Cl-amidine, a PAD4 inhibitor, but not by the NADPH inhibitor diphenyleneiodonium (DPI). Ponatinib pre-exposure significantly increased H3cit expression in HoxB8-BCR-ABL1 cells after stimulation with IO. In summary, CML is associated with increased NET formation, which is augmented by ponatinib, suggesting a possible role for NETs in promoting vascular toxicity in CML.

Vascular Endothelial Growth Factor, Soluble Fms-Like Tyrosine Kinase 1, and the Severity of Coronary Artery Disease

Angiology ◽  
2010 ◽  
Vol 62 (2) ◽  
pp. 176-183 ◽  
Author(s):  
Soo-Young Kim ◽  
Sang-Hak Lee ◽  
Sungha Park ◽  
Seok-Min Kang ◽  
Namsik Chung ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Vascular Endothelial Growth Factor ◽  
Coronary Artery ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Vascular Endothelial ◽  
Artery Disease ◽  
Endothelial Growth Factor
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