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1.
Commun Biol ; 5(1): 1044, 2022 10 01.
Article in English | MEDLINE | ID: mdl-36183045

ABSTRACT

Blood vessel branch points exhibiting oscillatory/turbulent flow and lower wall shear stress (WSS) are the primary sites of atherosclerosis development. Vascular endothelial functions are essentially dependent on these tangible biomechanical forces including WSS. Herein, we explored the influence of blood vessel bifurcation angles on hemodynamic alterations and associated changes in endothelial function. We generated computer-aided design of a branched human coronary artery followed by 3D printing such designs with different bifurcation angles. Through computational fluid dynamics analysis, we observed that a larger branching angle generated more complex turbulent/oscillatory hemodynamics to impart minimum WSS at branching points. Through the detection of biochemical markers, we recorded significant alteration in eNOS, ICAM1, and monocyte attachment in EC grown in microchannel having 60o vessel branching angle which correlated with the lower WSS. The present study highlights the importance of blood vessel branching angle as one of the crucial determining factors in governing atherogenic-endothelial dysfunction.


Subject(s)
Coronary Vessels , Models, Cardiovascular , Endothelial Cells , Hemodynamics , Humans , Stress, Mechanical
2.
J Cell Physiol ; 237(1): 992-1012, 2022 01.
Article in English | MEDLINE | ID: mdl-34520565

ABSTRACT

Histone protein modifications control the inflammatory state of many immune cells. However, how dynamic alteration in histone methylation causes endothelial inflammation and apoptosis is not clearly understood. To examine this, we explored two contrasting histone methylations; an activating histone H3 lysine 4 trimethylation (H3K4me3) and a repressive histone H3 lysine 27 trimethylation (H3K27me3) in endothelial cells (EC) undergoing inflammation. Through computer-aided reconstruction and 3D printing of the human coronary artery, we developed a unique model where EC were exposed to a pattern of oscillatory/disturbed flow as similar to in vivo conditions. Upon induction of endothelial inflammation, we detected a significant rise in H3K4me3 caused by an increase in the expression of SET1/COMPASS family of H3K4 methyltransferases, including MLL1, MLL2, and SET1B. In contrast, EC undergoing inflammation exhibited truncated H3K27me3 level engendered by EZH2 cytosolic translocation through threonine 367 phosphorylation and an increase in the expression of histone demethylating enzyme JMJD3 and UTX. Additionally, many SET1/COMPASS family of proteins, including MLL1 (C), MLL2, and WDR5, were associated with either UTX or JMJD3 or both and such association was elevated in EC upon exposure to inflammatory stimuli. Dynamic enrichment of H3K4me3 and loss of H3K27me3 at Notch-associated gene promoters caused ADAM17 and Jagged-1 derepression and abrupt Notch activation. Conversely, either reducing H3K4me3 or increasing H3K27me3 in EC undergoing inflammation attenuated Notch activation, endothelial inflammation, and apoptosis. Together, these findings indicate that dynamic chromatin modifications may cause an inflammatory and apoptotic switch of EC and that epigenetic reprogramming can potentially improve outcomes in endothelial inflammation-associated cardiovascular diseases.


Subject(s)
Histones , Lysine , ADAM17 Protein/metabolism , Endothelial Cells/metabolism , Histones/genetics , Histones/metabolism , Humans , Inflammation/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Jagged-1 Protein/genetics , Jagged-1 Protein/metabolism , Lysine/metabolism
3.
Sci Rep ; 9(1): 11139, 2019 07 31.
Article in English | MEDLINE | ID: mdl-31366988

ABSTRACT

Cataract is a common ophthalmic disorder and the leading cause of blindness worldwide. While cataract is cured via surgical procedures, its impact on iris based biometric recognition has not been effectively studied. The key objective of this research is to assess the effect of cataract surgery on the iris texture pattern as a means of personal authentication. We prepare and release the IIITD Cataract Surgery Database (CaSD) captured from 132 cataract patients using three commercial iris sensors. A non-comparative non-randomized cohort study is performed on the iris texture patterns in CaSD and authentication performance is studied using three biometric recognition systems. Performance is lower when matching pre-operative images to post-operative images (74.69 ± 9.77%) as compared to matching pre-operative images to pre-operative images (93.42 ± 1.76%). 100% recognition performance is observed on a control-group of healthy irises from 68 subjects. Authentication performance improves if cataract affected subjects are re-enrolled in the system, though re-enrollment does not ensure performance at par with pre-operative scenarios (86.67 ± 5.64%). The results indicate that cataract surgery affects the discriminative nature of the iris texture pattern. This finding raises concerns about the reliability of iris-based biometric recognition systems in the context of subjects undergoing cataract surgery.


Subject(s)
Cataract/physiopathology , Iris/physiopathology , Pattern Recognition, Physiological/physiology , Biometric Identification/methods , Biometry/methods , Cohort Studies , Female , Humans , Lens, Crystalline/physiopathology , Male , Pattern Recognition, Automated/methods , Phacoemulsification/methods , Reproducibility of Results
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