Aastha Mishra

Institute of Genomics and Integrative Biology | IGIB · Genomics and Molecular Medicine Research Area (IGIB)

The effect of high altitude (HA, altitude >2500 m) can trigger a maladaptive response in unacclimatized individuals, leading to various HA illnesses such as high altitude pulmonary edema (HAPE). The present study investigates circulating cell free (cf) DNA, a minimally invasive biomarker that can elicit a pro-inflammatory response. Our earlier stud...

Thrombosis, a coagulation disorder, occurs due to altered levels of coagulation, fibrinolytic and immune factors, which are otherwise known to maintain hemostasis in normal physiological conditions. Here, we review the direct and indirect participation of a multifunctional nuclear enzyme poly (ADP-ribose) polymerase-1 (PARP1) in the expression of k...

Background objectives: The Omicron sub-lineages are known to have higher infectivity, immune escape and lower virulence. During December 2022 - January 2023 and March - April 2023, India witnessed increased SARS-CoV-2 infections, mostly due to newer Omicron sub-lineages. With this unprecedented rise in cases, we assessed the neutralization potenti...

The utility of cell free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for utilizing its full potential. The high altitude (HA; altitude >250...

Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the pathophysiology of thrombosis, a process termed immune-thrombosis. Still, the shared underlying molecular...

Acute high-altitude (HA) exposure can induce several pathologies. Dexamethasone (DEX) can be taken prophylactically to prevent HA disease, but the mechanism by which it acts in this setting is unclear. We studied the transcriptome of peripheral blood mononuclear cells (PBMCs) from 16 subjects at low altitude (LA, 225m) and then 3 days after acute t...

Over the past several years, the Muzaffarpur district of Bihar (India) has witnessed recurrent outbreaks of acute encephalitis illness of unknown etiology, called acute encephalitis syndrome (AES) among young children, especially during the peak-summer season. Pesticide exposure, viral encephalitis, and litchi toxin intake have all been postulated...

Objective Exploration of the underlying molecular mechanisms between inflammation and coagulation pathways using publicly available transcriptome datasets of inflammatory disorders with pro-thrombotic phenotypic features. Methods Publicly available mRNA and miRNA expression datasets of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA),...

The dramatic changes in physiology at high altitude (HA) as a result of the characteristic hypobaric hypoxia condition can modify innate and adaptive defense mechanisms of the body. As a consequence, few sojourners visiting HA with mild or asymptomatic infection may have an enhanced susceptibility to high-altitude pulmonary edema (HAPE), an acute b...

Background High-altitude (HA, 2500 m) hypoxic exposure evokes a multitude of physiological processes. The hypoxia-sensing genes though influence transcriptional output in disease susceptibility; the exact regulatory mechanisms remain undetermined in high-altitude pulmonary edema (HAPE). Here, we investigated the differential DNA methylation distrib...

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may result in an overactive coagulative system, thereby resulting in serious cardiovascular consequences in critically affected patients. The respiratory tract is a primary target for COVID-19 infection, which is manifested as acute...

Thrombosis remains one of the leading causes of morbidity and mortality across the world. Many pathological milieus in the body resulting from multiple risk factors escort thrombosis. Hypoxic condition is one such risk factor that disturbs the integrity of endothelial cells to cause an imbalance between anticoagulant and procoagulant proteins. Hypo...

Thrombospondin-1 (THBS1) levels elevate under hypoxia and have relevance in several cardiovascular disorders. The association of THBS1 with endothelial dysfunction implies its important role in hypertension. To establish the hypothesis, we screened patients with hypertension and their respective controls from the two different environmental regions...

High-altitude (HA, > 2500 meters) hypoxic exposure evokes several physiological processes that may be abetted by differential genetic distribution in sojourners, who are susceptible to various HA disorders, such as high-altitude pulmonary edema (HAPE). The genetic variants in hypoxia-sensing genes influence the transcriptional output, however the f...

Vitamin D known for its vital role in diverse biological function such as calcium and phosphorus homeostasis, also exert an anticoagulant effect emphasizing its essential role in the thrombosis pathogenesis. Thrombosis is the formation and propagation of a blood clot or thrombus either in the arterial or the venous system resulting in several sever...

Severe novel corona virus disease 2019 (COVID-19) infection is associated with a considerable activation of coagulation pathways, endothelial damage, and subsequent thrombotic microvascular injuries. These consistent observations may have serious implications for the treatment and management of this highly pathogenic disease. As a consequence, the...

Hypobaric hypoxia poses stress to sojourners traveling to high-altitude (HA). A cascade of physiological changes occurs to cope with or adapt to hypobaric hypoxia. However, an insufficient physiological response to the hypoxic condition due to imbalanced vascular homeostasis pathways results in high-altitude pulmonary edema (HAPE). The present stud...

Cardiovascular Diseases (CVDs) as a leading cause of death worldwide inflict major stress on morbidity and societal costs. Though the studies pertaining to pathophysiology and genetics of CVDs have helped in prevention, diagnosis and treatment of diseases, there are still lacunas in our knowledge. So, novel tools that can define genomic regulation...

Inflammasome complex is a multimeric protein comprising of upstream sensor protein of nucleotide-binding oligomerization domain (NOD)-like receptor family. It has an adaptor protein apoptosis-associated speck-like protein and downstream effector cysteine protease procaspase-1. Activation of inflammasome complex is body’s innate response to pathogen...

Vitamin D, besides having an essential role in calcium and bone metabolism, also acts as a mediator of many non-calcemic effects through modulations of several biological responses. Vitamin D exists in its two major forms, vitamin D2, or commonly known as ergocalciferol, and vitamin D3, or commonly known as cholecalciferol. Both of these forms bind...

Thrombosis development in either arterial or venous system remains a major cause of death and disability worldwide. This poorly controlled in vivo clotting could result in many severe complications including myocardial infarction, venous thromboembolism, stroke, and cerebral venous thrombosis, to name a few. These conditions are collectively known...

Significance Exposure to a high-altitude (HA) hypobaric hypoxia environment produces physiological changes. Among these, the changes in the apelin signaling system are significant because this system regulates vascular and oxygen homeostasis. This study demonstrates that the HA environment stimulates the apelin system to distinguish genetic variant...

Hypobaric hypoxia at high-altitude (HA) results in reduced blood arterial oxygen saturation, perfusion of organs with hypoxemic blood and direct hypoxia of lung tissues. The pulmonary complications in the cells of the pulmonary arterioles due to hypobaric hypoxia are the basis of the pathophysiological mechanisms of high-altitude pulmonary edema (H...

Background: This study investigates the contribution of genetic interactions between the β-2 adrenergic receptor (ADRB2) and nitric oxide synthase (NOS3) genes to the complex etiology of hypertension. Methods: Using single nucleotide polymorphism (SNP) markers, we studied potential interactions between ADRB2 and NOS3 variants and their correlati...

High-altitude (HA) populations living for several thousands of years at elevations up to 5,000 m present many adaptive phenotypic changes; conversely, the lowland populations respond differentially like acclimatizing to the environment or predisposing to HA disorders. Hypobaric hypoxia environment at HA results into reduced blood arterial O2 satura...

EGLN1 [encoding HIF (hypoxia-inducible factor)-prolyl hydroxylase 2] plays a pivotal role in the HIF pathway and has emerged as one of the most intriguing genes with respect to physiology at HA (high altitude). EGLN1, being an actual oxygen sensor, appears to have a potential role in the functional adaptation to the hypobaric hypoxic environment. I...

HIF-prolyl hydroxylase 2 (EGLN1) plays a pivotal role in hypoxia-inducible factor pathway and has emerged as the most intriguing gene with respect to high-altitude (HA). EGLN1, being an actual oxygen sensor seems to have a potential role in the functional adaptation to hypobaric hypoxic environment. This study, therefore, screened 30 polymorphisms...

The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in comparison to HAPE-free sojourners (HAPE-f)...

(a–b): Correlation analyses between NO and clinical parameters in the three groups i.e. HAPE-p, HAPE-f and HLs. Proportional or inverse correlations were obtained between a) NO, µmol/mL and SaO2, %; b) NO, µmol/mL and MAP, mmHg. (TIF)

(a–i): Correlation analyses among biochemical parameters in the three groups i.e. HAPE-p, HAPE-f and HLs. Proportional or inverse correlations were obtained between a) ADMA, nmol/mL and 5-HT, ng/mL; b) ADMA, nmol/mL and SOD, U/mL; c) ADMA, nmol/mL and 8-isoPGF2α, pg/mL; d) SOD, U/mL and ET-1, pg/mL; e) 5-HT, ng/mL and ET-1, pg/mL; f) and 8-isoPGF2α...

Real-Time PCR conditions for TPH-1 , ET-1 , REN , CYP11B2 , SOD and NOS3 . (DOC)

(a–e): Correlation analyses among biochemical parameters with NO in the three groups i.e. HAPE-p, HAPE-f and HLs. Proportional or inverse correlations were obtained between a) NO, µmol/mL and ADMA, nmol/mL; b) NO, µmol/mL and 5-HT, ng/mL; c) NO, µmol/mL and 8-isoPGF2α, pg/mL; d) NO, µmol/mL and SOD, U/mL; e) NO, µmol/mL and ET-1, pg/mL. (TIF)

(a–g): Correlation analyses between biochemical parameters and clinical parameters in the three groups i.e. HAPE-p, HAPE-f and HLs. Proportional or inverse correlations were obtained between a) ADMA, nmol/mL and SaO2, %; b) 5-HT, ng/mL and SaO2,%; c) 8-isoPGF2α, pg/mL and SaO2, %; d) SOD, U/mL and SaO2, %; e) ADMA, nmol/mL and MAP, mmHg; f) 8-isoPG...

(a–c): Multiple regression analysis in the three groups i.e. HAPE-p, HAPE-f and HLs. The boxes with shades of red depicted positive correlations and boxes with shades of green depicted inverse correlations. Each box contains the coefficient of correlation along with p value. The p value was calculated placing one biomarker against all the studied b...

Residents of Himalayas have evidence of selection of genetic variants and the genes of oxygen sensing pathway have emerged favorite candidates. Candidate gene and genome‐wide association studies (GWAS) have substantiated the involvement of endothelial PAS domain‐containing protein 1 (EPAS1) and HIF‐1 prolyl hydroxylase 2 (EGLN1) in adaptation to an...

HAPE (high-altitude pulmonary oedema) is characterized by pulmonary hypertension, vasoconstriction and an imbalance in oxygen-sensing redox switches. Excess ROS (reactive oxygen species) contribute to endothelial damage under hypobaric hypoxia, hence the oxidative-stress-related genes CYBA (cytochrome b-245 α polypeptide) and GSTP1 (glutathione tra...

The genetic susceptibility to chronic obstructive pulmonary disease (COPD) depends on detoxification and antioxidant enzymes, which detoxify cigarette smoke reactive components that, otherwise, generate oxidative stress. In a case-control study of 346 subjects with and without COPD, we examined the polymorphisms 462Ile/Val, 3801T/C of CYP1A1, -3860...