aastha mishra - Academia.edu (original) (raw)
Papers by aastha mishra
TH Open, 2022
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronaviru... more 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 lung injury in the most severe form of the viral infection, leading to respiratory failure. A proportion of infected patients may progress to serious systemic disease including dysfunction of multiple organs, acute respiratory distress syndrome (ARDS), and coagulation abnormalities, all of which are associated with increased mortality, additionally depending on age and compromised immunity. Coagulation abnormalities associated with COVID-19 mimic other systemic coagulopathies otherwise involved in other severe infections, such as disseminated intravascular coagulation (DIC) and may be termed COVID-19 induced coagulopathy (CIC). There is s...
Cardiovascular Diseases (CVDs) as a leading cause of death worldwide inflict major stress on morb... more 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 under different conditions are needed to bridge this gap. 'Epigenetic' mechanism helps the cells to quickly respond to ever changing environment by molecular mechanisms like methylation, histone modifications, nc-RNAs. These mechanisms act as a new layer of regulation in CVDs. The role of epigenetics as a key regulatory player in prevention, diagnosis and treatment of CVDs is emerging. Thus, the focus of present chapter is to decipher the role of epigenetics in CVDs and its potential to be used in risk assessment or as biomarkers in devising and deploying better diagnosis and treatment for different CVDs.
Frontiers in Physiology, 2021
Thrombosis remains one of the leading causes of morbidity and mortality across the world. Many pa... more 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. Hypoxia generates reactive oxygen species (ROS) and triggers inflammatory pathways to augment the coagulation cascade. Hypoxia in cells also activates unfolded protein response (UPR) signaling pathways in the endoplasmic reticulum (ER), which tries to restore ER homeostasis and function. But the sustained UPR linked with inflammation, generation of ROS and apoptosis stimulates the severity of thrombosis in the body. Sirtuins, a group of seven proteins, play a vast role in bringing down inflammation, oxidative and ER stress and apoptosis. As a result, sirtuins might provide a therapeutic approach towards the treatment or prevention of hypoxia-i...
Vitamin D, 2021
Vitamin D known for its vital role in diverse biological function such as calcium and phosphorus ... more 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 severe complications. Various studies have also reported the association of vitamin D deficiency with the increased incidences of thromboembolism. This may be in part due to its anticoagulant effects through upregulation of thrombomodulin, an anticoagulant glycoprotein, and downregulation of Tissue Factor, a critical coagulation factor. The protective effects of vitamin D and its receptor in endothelial cells may further explain some of the reported beneficial effects of vitamin D in the prevention or treatment of cardiovascular diseases. Additionally, the immunomodulatory role of vitamin D has been observed through its ability to alter the sec...
TH Open, 2020
Severe novel corona virus disease 2019 (COVID-19) infection is associated with a considerable act... more 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 anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of ...
Seminars in Thrombosis and Hemostasis, 2021
Frontiers in Cell and Developmental Biology, 2020
Inflammasome complex is a multimeric protein comprising of upstream sensor protein of nucleotide-... more 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 attack but its abnormal activation results in many inflammatory and cardiovascular disorders including thrombosis. It has displayed a prominent role in the clot formation advocating an interplay between inflammation and coagulation cascades. Therefore, elucidation of inflammasome and its molecular mechanisms in the manifestation of prothrombotic phenotypes becomes pertinent. Thrombosis is the formation and propagation of blood clot in the arterial or venous system due to several interactions of vascular and immune factors. It is a prevalent pathology underlying disorders like venous thromboembolism, stroke and acute coronary syndrome; thus, making thrombosis, a major contributor to the global disease burden. Recently studies have established a strong connection of inflammatory processes with this blood coagulation disorder. The hemostatic balance in thrombosis gets altered by the inflammatory mechanisms resulting in endothelial and platelet activation that subsequently increases secretion of several prothrombotic and antifibrinolytic factors. The upregulation of these factors is the critical event in the pathogenesis of thrombosis. Among various inflammasome, nucleotide-binding domain, leucine-richcontaining family, pyrin domain containing 3 (NLRP3) is one of the best-studied sterile inflammasome strengthening a link between inflammation and coagulation in thrombosis. NLRP3 activation results in the catalytic conversion of procaspase-1 to active caspase-1, which facilitate the maturation of interleukin-1β (IL-1β) and interleukin-18. These cytokines are responsible for immune cells activation critical for immune responses. These responses further results in endothelial and platelet activation and aggregation. However, the exact molecular mechanism related to the pathogenesis of thrombosis is still elusive. There have been several reports that demonstrate Tissue factor (TF)-mediated signaling in the production of pro-inflammatory cytokines enhancing inflammation by activating protease-activated receptors on various cells,
Seminars in Thrombosis and Hemostasis, 2019
Thrombosis development in either arterial or venous system remains a major cause of death and dis... more 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 as thromboembolic disorders (TEDs). Appropriate understanding of TEDs is challenging, as they are multifactorial and involve several and often different risk factors. Hence, it requires a collective effort and data from numerous research studies to fully comprehend molecular mechanisms for prediction, prevention, treatment, and overall management of these conditions. To accomplish this arduous feat, a comprehensive approach is required that can compile thousands of available experimental data and transform these into more applicable and purposeful findings. Thus, large datasets could be utilized to generate models that could be predictive ...
TH Open, 2022
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronaviru... more 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 lung injury in the most severe form of the viral infection, leading to respiratory failure. A proportion of infected patients may progress to serious systemic disease including dysfunction of multiple organs, acute respiratory distress syndrome (ARDS), and coagulation abnormalities, all of which are associated with increased mortality, additionally depending on age and compromised immunity. Coagulation abnormalities associated with COVID-19 mimic other systemic coagulopathies otherwise involved in other severe infections, such as disseminated intravascular coagulation (DIC) and may be termed COVID-19 induced coagulopathy (CIC). There is s...
Cardiovascular Diseases (CVDs) as a leading cause of death worldwide inflict major stress on morb... more 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 under different conditions are needed to bridge this gap. 'Epigenetic' mechanism helps the cells to quickly respond to ever changing environment by molecular mechanisms like methylation, histone modifications, nc-RNAs. These mechanisms act as a new layer of regulation in CVDs. The role of epigenetics as a key regulatory player in prevention, diagnosis and treatment of CVDs is emerging. Thus, the focus of present chapter is to decipher the role of epigenetics in CVDs and its potential to be used in risk assessment or as biomarkers in devising and deploying better diagnosis and treatment for different CVDs.
Frontiers in Physiology, 2021
Thrombosis remains one of the leading causes of morbidity and mortality across the world. Many pa... more 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. Hypoxia generates reactive oxygen species (ROS) and triggers inflammatory pathways to augment the coagulation cascade. Hypoxia in cells also activates unfolded protein response (UPR) signaling pathways in the endoplasmic reticulum (ER), which tries to restore ER homeostasis and function. But the sustained UPR linked with inflammation, generation of ROS and apoptosis stimulates the severity of thrombosis in the body. Sirtuins, a group of seven proteins, play a vast role in bringing down inflammation, oxidative and ER stress and apoptosis. As a result, sirtuins might provide a therapeutic approach towards the treatment or prevention of hypoxia-i...
Vitamin D, 2021
Vitamin D known for its vital role in diverse biological function such as calcium and phosphorus ... more 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 severe complications. Various studies have also reported the association of vitamin D deficiency with the increased incidences of thromboembolism. This may be in part due to its anticoagulant effects through upregulation of thrombomodulin, an anticoagulant glycoprotein, and downregulation of Tissue Factor, a critical coagulation factor. The protective effects of vitamin D and its receptor in endothelial cells may further explain some of the reported beneficial effects of vitamin D in the prevention or treatment of cardiovascular diseases. Additionally, the immunomodulatory role of vitamin D has been observed through its ability to alter the sec...
TH Open, 2020
Severe novel corona virus disease 2019 (COVID-19) infection is associated with a considerable act... more 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 anticoagulant therapeutic strategies, such as low molecular weight heparin, have shown some encouraging results. Cytokine burst leading to sepsis which is one of the primary reasons for acute respiratory distress syndrome (ARDS) drive that could be worsened with the accumulation of coagulation factors in the lungs of COVID-19 patients. However, the obscurity of this syndrome remains a hurdle in making decisive treatment choices. Therefore, an attempt to characterize shared biological mechanisms between ARDS and thrombosis using comprehensive transcriptomics meta-analysis is made. We conducted an integrated gene expression meta-analysis of ...
Seminars in Thrombosis and Hemostasis, 2021
Frontiers in Cell and Developmental Biology, 2020
Inflammasome complex is a multimeric protein comprising of upstream sensor protein of nucleotide-... more 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 attack but its abnormal activation results in many inflammatory and cardiovascular disorders including thrombosis. It has displayed a prominent role in the clot formation advocating an interplay between inflammation and coagulation cascades. Therefore, elucidation of inflammasome and its molecular mechanisms in the manifestation of prothrombotic phenotypes becomes pertinent. Thrombosis is the formation and propagation of blood clot in the arterial or venous system due to several interactions of vascular and immune factors. It is a prevalent pathology underlying disorders like venous thromboembolism, stroke and acute coronary syndrome; thus, making thrombosis, a major contributor to the global disease burden. Recently studies have established a strong connection of inflammatory processes with this blood coagulation disorder. The hemostatic balance in thrombosis gets altered by the inflammatory mechanisms resulting in endothelial and platelet activation that subsequently increases secretion of several prothrombotic and antifibrinolytic factors. The upregulation of these factors is the critical event in the pathogenesis of thrombosis. Among various inflammasome, nucleotide-binding domain, leucine-richcontaining family, pyrin domain containing 3 (NLRP3) is one of the best-studied sterile inflammasome strengthening a link between inflammation and coagulation in thrombosis. NLRP3 activation results in the catalytic conversion of procaspase-1 to active caspase-1, which facilitate the maturation of interleukin-1β (IL-1β) and interleukin-18. These cytokines are responsible for immune cells activation critical for immune responses. These responses further results in endothelial and platelet activation and aggregation. However, the exact molecular mechanism related to the pathogenesis of thrombosis is still elusive. There have been several reports that demonstrate Tissue factor (TF)-mediated signaling in the production of pro-inflammatory cytokines enhancing inflammation by activating protease-activated receptors on various cells,
Seminars in Thrombosis and Hemostasis, 2019
Thrombosis development in either arterial or venous system remains a major cause of death and dis... more 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 as thromboembolic disorders (TEDs). Appropriate understanding of TEDs is challenging, as they are multifactorial and involve several and often different risk factors. Hence, it requires a collective effort and data from numerous research studies to fully comprehend molecular mechanisms for prediction, prevention, treatment, and overall management of these conditions. To accomplish this arduous feat, a comprehensive approach is required that can compile thousands of available experimental data and transform these into more applicable and purposeful findings. Thus, large datasets could be utilized to generate models that could be predictive ...