Page 36 - Annual report 2021-22

Annual Report 2021-22 |

Aastha Mishra

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Aastha Mishra’s lab works in the area of hypoxia adaptation.

Hypoxia has been linked with inflammation and activation of many cells such as endothelium, platelets
and lymphocytes causing homeostatic imbalance, secretion of pro-thrombotic and antifibrinolytic
factors. Her lab studies hypoxia induced thrombosis using a cellular model where human umbilical
endothelial cell line (HUVEC) is exposed to thrombin and 1% oxygen environment. Hypoxia markers
such as hypoxia inducible factor--1 alpha (HIF-1alpha), prolyl hydroxylase-1 (PHD2) and prothrombotic
markers such as caspase 4, VCAM-1, E-selectin, P-selectin, Factor-2 were assessed for the validation
of their hypoxia-induced in vitro thrombosis model. The markers were compared to the cells not
subjected to thrombin or hypoxia. An induction of all these markers occurred due to hypoxia and
thrombin exposure. Future studies aim to identify the role of HIF1alpha in this process. Findings from
these studies will also be tested in high altitude exposed hypoxia. Both cases and controls (lowlanders
and highlanders) will be collected and demographic as well as clinical profiles will be carried out for
each blood sample.

Aastha’s work extends to understand the interplay between unfolded protein response (UPR) and
inflammatory pathways in hypoxia-induced thromboembolic disorders. Hypoxia is a condition in which
oxygen level in the cells or tissues decreases leading to activation of HIF-1 alpha, reactive oxygen
species (ROS) and inflammation. These factors contribute to endothelial cell dysfunction, activation
and an imbalance between procoagulant and anticoagulant proteins. All these pathophysiological
conditions in the body can lead to thrombosis. Thrombosis is a complex process of formation of blood
clots inside blood vessels leading to obstruction in blood flow. Additionally, hypoxia also contributes
to the accumulation of misfolded proteins in endoplasmic reticulum (ER) lumen because of
disturbance in oxidative protein folding leading to ER stress. Activation of chronic UPR leads to
endothelial cell dysfunction, a crucial feature of hypoxia induced thrombosis. Her group has found
induction of the UPR in the cellular model of hypoxia and thrombin exposure. Further studies will be
aimed at understanding the role of the inflammatory response on the induction of UPR.