Article
Cardiac & Cardiovascular Systems
Benjamin Grimmer, Adrienn Krauszman, Xudong Hu, Golam Kabir, Kim A. Connelly, Mei Li, Jana Grune, Christian Madry, Brant E. Isakson, Wolfgang M. Kuebler
Summary: This study identifies Panx1 as a novel regulator of HPV, but its role is not necessarily linked to ATP release and downstream signaling via P2Y receptors or TRPV4 activation. Instead, Panx1 appears to modulate the Ca2+ response of PASMC to hypoxia. Furthermore, Panx1 does not affect the development of chronic hypoxic PH.
CARDIOVASCULAR RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Alejandro Gutierrez, Alfonso Gomez del Val, Cristina Contreras, Lucia Olmos, Ana Sanchez, Dolores Prieto
Summary: Abnormal endothelin-1 (ET-1) activity is involved in the pathogenesis of various vascular diseases. The inhibition of ET receptors has shown efficacy in clinical and experimental models. Peripheral resistance arteries play a key role in blood pressure regulation, and the study aimed to determine the Ca2+ signaling mechanisms involved in ET receptor-mediated vasoconstriction. ET-1-induced contraction in resistance arteries is mediated by the ETA receptor and involves Ca2+ mobilization, extracellular Ca2+ influx, and Ca2+ sensitization.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Physiology
Tyler Kelly, Courtney Brown, Mohini Bryant-Ekstrand, Rachel Lord, Tony Dawkins, Aimee Drane, Joel E. Futral, Otto Barak, Tanja Dragun, Michael Stembridge, Boris Spajic, Ivan Drvis, Joseph W. Duke, Philip N. Ainslie, Glen E. Foster, Zeljko Dujic, Andrew T. Lovering
Summary: This study aimed to investigate the pulmonary vasoreactivity and right heart work in apnoea divers under the stress of hyperbaric, hypercapnic, acidotic, and hypoxic conditions. The findings showed that divers experienced less change in total pulmonary resistance compared to the control group during short-duration isocapnic hypoxia. The administration of sildenafil had a similar effect on reducing pulmonary resistance in both divers and controls. This suggests that divers can maintain normal pulmonary artery tone in hypoxic conditions, which might be a beneficial adaptation for apnoea diving.
EXPERIMENTAL PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Mike Stembridge, Ryan L. Hoiland, Alexandra M. Williams, Connor A. Howe, Joseph Donnelly, Tony G. Dawkins, Aimee Drane, Michael M. Tymko, Christopher Gasho, James Anholm, Lydia L. Simpson, Jonathan P. Moore, Damian M. Bailey, David B. MacLeod, Philip N. Ainslie
Summary: The study demonstrates that hemodilution can impact hypoxic pulmonary vasoconstriction (HPV) through increased frictional force and vasoactive signaling from erythrocytes. The balance of these mechanisms is influenced by the duration of hypoxia exposure and hematocrit level. While hemodilution mildly increased pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) at sea level, it did not significantly alter these parameters at high altitude, where both remained sensitive to additional acute hypoxia. In Andean high-altitude natives with excessive erythrocytosis, hemodilution lowered PVR but did not change PASP due to compensatory increase in cardiac output.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Article
Neurosciences
Christopher K. Willie, Alexander Patrician, Ryan L. Hoiland, Alexandra M. Williams, Christopher Gasho, Prajan Subedi, James Anholm, Aimee Drane, Michael M. Tymko, Daniela Nowak-Fluck, Sawyer Plato, Emily McBride, Giovanfrancesco Varoli, Gordon Binsted, Lindsay K. Eller, Raylene A. Reimer, David B. MacLeod, Michael Stembridge, Philip N. Ainslie
Summary: Iron plays an influential role in the modulation of hypoxic pulmonary vasoconstriction at high altitude. Lowerlanders experienced a more significant reduction in iron bioavailability compared to Sherpa during ascent to 5050 m. Iron infusion attenuated PASP at rest, while chelation did not exacerbate PASP during rest or exaggerated hypoxemia.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Cardiac & Cardiovascular Systems
Xizhong Cui, Jeffrey Wang, Yan Li, Zoe G. Couse, Thomas F. Risoleo, Mahtab Moayeri, Stephen H. Leppla, Daniela Malide, Zu-Xi Yu, Peter Q. Eichacker
Summary: This study shows that Bacillus anthracis edema toxin can inhibit hypoxic pulmonary vasoconstriction, potentially worsening hypoxemia during invasive anthrax lung infection. The findings suggest that both edema toxin and lethal toxin can contribute to pulmonary pathophysiology during infection, highlighting the importance of antitoxin therapies in managing severe anthrax disease.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Karem Arriaza, Constanza Cuevas, Eduardo Pena, Patricia Siques, Julio Brito
Summary: This review investigates the relationship between altered zinc (Zn2+) levels and oxidative stress in hypoxic pulmonary vasoconstriction (HPV) under hypobaric hypoxic conditions. The results suggest that elevated Zn2+ levels are associated with increased mitochondrial ROS, nitric oxide, metallothionein, zinc-regulated iron-regulated transporter-like protein, and NADPH oxidase-induced PKC ε activation in the development of HPV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Yuting Xie, Lin Yue, Yaojie Shi, Xingping Su, Cailing Gan, Hongyao Liu, Taixiong Xue, Tinghong Ye
Summary: Pulmonary fibrosis is a lethal disease with limited therapeutic options. ROCK activation has been observed in PF patients and animal models, making it a promising target for treatment. Although many ROCK inhibitors have been discovered and approved for clinical use, none are approved for PF treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Peripheral Vascular Disease
Yuqing Shi, Jie Liu, Ruoyang Zhang, Muzhi Zhang, Han Cui, Lei Wang, Ye Cui, Wei Wang, Ying Sun, Chen Wang
Summary: It has been shown that glycolytic protein ENO1 contributes to the pathogenesis of pulmonary hypertension by acting on smooth muscle cells. However, the specific roles of ENO1 in endothelial and mitochondrial dysfunctions in Group 3 pulmonary hypertension have not been explored. This study revealed that hypoxic pulmonary hypertension is associated with increased ENO1 expression and targeting ENO1 can reduce hypoxic pulmonary hypertension by improving endothelial and mitochondrial dysfunction via the PI3K-Akt-mTOR signaling pathway.
Article
Biochemistry & Molecular Biology
Krishna C. Penumatsa, Adit A. Singhal, Rod R. Warburton, Michael D. Bear, Chinmayee D. Bhedi, Sabina Nasirova, Jamie L. Wilson, Guanming Qi, Ioana R. Preston, Nicholas S. Hill, Barry L. Fanburg, Young-Bum Kim, Deniz Toksoz
Summary: The study demonstrates that ROCK1 plays a role in the development of pulmonary arterial hypertension (PAH) through nonproliferative pathways, contributing to hypoxemia. The findings suggest that ROCK1 may be a distinct therapeutic target in PAH.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Weibin Zhou, Keli Liu, Lei Zeng, Jiaqi He, Xinbo Gao, Xinyu Gu, Xun Chen, Jing Jing Li, Minghui Wang, Duoguang Wu, Zhixiong Cai, Lena Claesson-Welsh, Rong Ju, Jingfeng Wang, Feng Zhang, Yangxin Chen
Summary: This study found that VEGF-A/VEGFR2 Y949-dependent vascular permeability plays a significant role in the pathogenesis of PH and may serve as an attractive therapeutic target pathway for this disease.
Review
Oncology
Tianci Chai, Chen Qiu, Zhihong Xian, Yongzhen Lu, Yuwei Zeng, Jie Li
Summary: The background, objective, methods, key content, and findings of a review on the diagnosis, pathogenesis, and treatment of hypoxic pulmonary hypertension (HPH) are summarized. The review highlights the importance of HPH in chronic obstructive pulmonary disease (COPD) and chronic mountain sickness (CMS) and provides an overview of the diagnosis, pathogenesis, and treatment options for HPH. However, despite progress in understanding the pathophysiology and molecular biology of HPH, there is still a lack of breakthroughs in treatment. Further research is needed to uncover the specific mechanisms and develop more effective targeted drugs.
ANNALS OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Aya Yamamura, Md Junayed Nayeem, Motohiko Sato
Summary: Enhanced ROCK2 signaling is involved in the pathogenic mechanism underlying the development of PAH, and ROCK2 may be a novel therapeutic target for the treatment of PAH, as its inhibitor KD025 effectively suppresses the proliferation of IPAH-PASMCs and attenuates the elevated right ventricular systolic pressure in MCT-PH rats.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Cardiac & Cardiovascular Systems
Helen Christou, Raouf A. Khalil
Summary: Pulmonary hypertension is a serious disease characterized by vasoconstriction and remodeling of the pulmonary arterioles, leading to increased pulmonary vascular resistance and right ventricular hypertrophy. Current pharmacological therapies focus on pulmonary vasodilation but are not universally successful. Therefore, researchers are exploring novel approaches to reverse pulmonary vascular pathology and structural remodeling.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Cecile Lebon, Heike Neubauer, Marianne Berdugo, Kimberley Delaunay, Elke Markert, Kolja Becker, Katja S. Baum-Kroker, Juergen Prestle, Holger Fuchs, Remko A. Bakker, Francine Behar-Cohen
Summary: The study showed that sustained ROCK inhibition provided by BIRKI slow-release formulation could be a valuable treatment option for diabetic retinopathy, especially with regard to the improvement of retinal vascular infusion and protection of the outer retinal barrier.
Article
Cardiac & Cardiovascular Systems
Rui Song, Xiang-Qun Hu, Monica Romero, Mark A. Holguin, Whitney Kagabo, Daliao Xiao, Sean M. Wilson, Lubo Zhang
Summary: Pregnancy increases the association of BKCa channel subunits and alters the localization of RyR subtypes in uterine arteries. Knockdown of RyR1 or RyR2 decreases Ca2+ sparks and STOCs frequency, increases myogenic tone, while RyR3 knockdown has no significant effect. This study provides new insights into the mechanisms of uterine vascular adaptation to pregnancy through RyR subtypes.
CARDIOVASCULAR RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Samiksha Wasnik, Xiaolei Tang, Hongzheng Bi, Amir Abdipour, Edmundo E. Carreon, Brian Sutjiadi, Justin Lyu, Jintao Zhang, Sean Wilson, David J. Baylink
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Physiology
Arlin B. Blood, Taiming Liu, George Mukosera, Shawn F. Hanson, Michael H. Terry, Hobe Schroeder, Gordon G. Power
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2020)
Article
Peripheral Vascular Disease
Xiang-Qun Hu, Rui Song, Monica Romero, Chiranjib Dasgupta, Joseph Min, Daisy Hatcher, Daliao Xiao, Arlin Blood, Sean M. Wilson, Lubo Zhang
Article
Physiology
Eric Leslie, Vanessa Lopez, Nana A. O. Anti, Rafael Alvarez, Isaac Kafeero, Donald G. Welsh, Monica Romero, Shawn Kaushal, Catherine M. Johnson, Remy Bosviel, Ivana Blazenovic, Rui Song, Alex Brito, Michael R. La Frano, Lubo Zhang, John W. Newman, Oliver Fiehn, Sean M. Wilson
Summary: The research demonstrates that long-term hypoxia in fetuses leads to metabolic reprogramming and phenotypic transformations in the pulmonary arteries of fetal sheep, potentially contributing to the development of persistent pulmonary hypertension.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Peripheral Vascular Disease
Xiang-Qun Hu, Chiranjib Dasgupta, Rui Song, Monica Romero, Sean M. Wilson, Lubo Zhang
Summary: Pregnancy-induced hypoxia significantly increases circulating levels of miR-210 in both ewes and their fetuses. The study revealed that miR-210 directly targets and downregulates specific proteins in uterine arteries, leading to significant decreases in Ca2+ sparks and STOCs. This mechanistic link sheds light on pregnancy complications associated with hypoxia and potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Kevin Munoz, Samiksha Wasnik, Amir Abdipour, Hongzheng Bi, Sean M. Wilson, Xiaolei Tang, Mahdis Ghahramanpouri, David J. Baylink
Summary: The study aimed to develop a treatment to normalize the excess production of inflammatory cytokines and promote tissue repair in LPS-induced ALI. Results showed that the combination therapy of IGF-I and BTP-2 improved lung injuries, decreased the expression of inflammatory mediators, and enhanced vascular gene expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Brenda L. Bartnik-Olson, Arlin B. Blood, Michael H. Terry, Shawn F. L. Hanson, Christopher Day, Daniel Kido, Paggie Kim
Summary: QSM-derived venous susceptibility is sensitive to cerebral oxygenation status across various oxygenation states and strongly correlated with brain tissue O2 tension, while showing no correlation with CBF.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Physiology
Casey Reid, Monica Romero, Stephanie B. Chang, Noah Osman, Jose L. Puglisi, Christopher G. Wilson, Arlin B. Blood, Lubo Zhang, Sean M. Wilson
Summary: The regulation of cerebral blood flow is essential for the cerebral arterial vasoreactivity. This study investigates the impact of age and long-term hypoxia on membrane depolarization and intracellular calcium signaling in cerebral arteries using fluorescence imaging techniques. The results show that both altitude and age play a role in affecting the whole-cell and localized calcium signaling, which are important factors for arterial vasoreactivity and cerebral blood flow.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xiang-Qun Hu, Rui Song, Chiranjib Dasgupta, Monica Romero, Rucha Juarez, Jenna Hanson, Arlin B. Blood, Sean M. Wilson, Lubo Zhang
Summary: This study demonstrates a novel mechanistic role for the miR-210-ISCU-mtROS axis in inhibiting Ca2+ sparks/STOCs in the maladaptation of uterine arteries and provides new insights into the understanding of mitochondrial perturbations in the pathogenesis of pregnancy complications resulted from hypoxia.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Antoine Nehme, Mahdis Ghahramanpouri, Iqbal Ahmed, Mohadese Golsorkhi, Natasha Thomas, Kevin Munoz, Amir Abdipour, Xiaolei Tang, Sean M. Wilson, Samiksha Wasnik, David J. Baylink
Summary: This study found that a combination therapy of IGF-I and BTP-2 can effectively modify and restore LPS-induced gene changes and reduce vascular leakage caused by LPS. Furthermore, IGF-I also promotes liver regeneration.
Article
Endocrinology & Metabolism
Matilda H-C Sheng, Kin-Hing William Lau, Charles H. Rundle, Anar Alsunna, Sean M. Wilson, David J. Baylink
Summary: This study reveals the mechanism of impaired osteoblast differentiation in aged bone cells, which is caused by reduced activation of SOCE. This finding is important for understanding the mechanism of fracture repair in the elderly.
JOURNAL OF BONE AND MINERAL METABOLISM
(2022)
Review
Physiology
James J. Yu, Amy L. Non, Erica C. Heinrich, Wanjun Gu, Joe Alcock, Esteban A. Moya, Elijah S. Lawrence, Michael S. Tift, Katie A. O'Brien, Jay F. Storz, Anthony Signore, Jane Khudyakov, William K. Milsom, Sean M. Wilson, Cynthia M. Beall, Francisco C. Villafuerte, Tsering Stobdan, Colleen G. Julian, Lorna G. Moore, Mark M. Fuster, Jennifer A. Stokes, Richard Milner, John B. West, Jiao Zhang, John Y. Shyy, Ainash Childebayeva, Jose Pablo Vazquez-Medina, Luu Pham, Omar A. Mesarwi, James E. Hall, Zachary A. Cheviron, Jeremy Sieker, Arlin B. Blood, Jason X. Yuan, Graham R. Scott, Brinda K. Rana, Paul J. Ponganis, Atul Malhotra, Frank L. Powell, Tatum S. Simonson
Summary: The ability to respond rapidly to changes in oxygen tension is critical for various life forms. This paper synthesizes research findings across different time scales, ranging from early animal to modern human evolution, to understand the mechanisms of hypoxia adaptation and tolerance. By using emerging multi-omics approaches, the potential impacts of environmental and clinical challenges on oxygen homeostasis are examined. The study explores how different animal species have adapted to hypoxic environments and how humans vary in their responses to hypoxia in different contexts, such as high-altitude exposure, cardiopulmonary disease, and sleep apnea. The findings from each field inform and guide new directions in basic and clinical hypoxia research.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Madison Boskind, Nikitha Nelapudi, Grace Williamson, Bobby Mendez, Rucha Juarez, Lubo Zhang, Arlin B. Blood, Christopher G. Wilson, Jose Luis Puglisi, Sean M. Wilson
Summary: Intracellular Ca2+ signals play a crucial role in regulating various cellular processes. However, analyzing stochastic and rapid subcellular Ca2+ responses is time-consuming and often requires visual analysis. This study aimed to automate the analysis of Ca2+ fluorescence data from vascular myocytes without introducing errors. The results showed that the automated analysis techniques were reliable, with no significant differences compared to manual analysis. This automated approach will improve the workflow of spatial and temporal analysis of Ca2+ imaging data.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Medicine, General & Internal
J. Bierwirth, T. Liu, B. Mendez, S. Bragg, G. Power, A. Blood
JOURNAL OF INVESTIGATIVE MEDICINE
(2020)