Review
Biochemistry & Molecular Biology
Max Liu, Khalequz Zaman, Yolanda M. Fortenberry
Summary: Aptamers are single-stranded DNA or RNA sequences that exhibit high specificity and affinity in binding target molecules. They are non-immunogenic, easier to synthesize and modify, and can bind targets with greater affinity, making them a promising therapeutic candidate for treating various conditions. Active research is ongoing in developing aptamers to target blood coagulation factors, with potential applications in treating cardiovascular diseases, blood disorders, and cancers. Although no aptamers targeting blood coagulation factors have been approved for clinical use, several have shown promise in clinical trials and preclinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Maria D. Valls, Maria Soldado, Jorge Arasa, Miguel Perez-Aso, Adrienne J. Williams, Bruce N. Cronstein, M. Antonia Noguera, M. Carmen Terencio, M. Carmen Montesinos
Summary: Activation of adenosine A(2A) receptor can promote angiogenesis by increasing the expression of annexin A2 in human dermal microvascular endothelial cells, which enhances fibrinolysis and contributes to wound healing and tissue revascularization.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kiyotaka Okada, Naoyuki Kawao, Daisho Nakai, Rei Wakabayashi, Yoshitaka Horiuchi, Katsumi Okumoto, Shinji Kurashimo, Yoshimasa Takafuji, Osamu Matsuo, Hiroshi Kaji
Summary: This study demonstrated that glucocorticoids decrease the number of macrophages at the injured site during early bone repair after femoral bone injury partly through PAI-1 and M-CSF in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Health Care Sciences & Services
Hee Young Cho, Han Sung Park, Eun Hee Ahn, Eun Ju Ko, Hyeon Woo Park, Young Ran Kim, Ji Hyang Kim, Woo Sik Lee, Nam Keun Kim
Summary: The study revealed that PAI-1 rs1050955 and REN 10795 rs5707 alleles may decrease the risk of RPL, while the tPA rs4646972 genotype may increase the risk of RPL.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Dermatology
Yu-Ju Tseng, Chih-Hung Lee, Wei-Yu Chen, Jenq-Lin Yang, Hong-Tai Tzeng
Summary: The study demonstrates that PAI-1 activity regulates immune checkpoints by promoting lysosomal degradation of PD-L1. Inhibition of PAI-1 combined with anti-PD-L1 immunotherapy shows promise as a therapeutic regimen for melanoma treatment.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Oncology
Hong-Tai Tzeng, Jenq-Lin Yang, Yu-Ju Tseng, Chih-Hung Lee, Wei-Ju Chen, I-Tsu Chyuan
Summary: Tumor autophagy dysregulation is associated with cancer development and chemotherapeutic response; Autophagy-dependent PAI-1 secretion contributes to melanoma resistance to mitoxantrone; Targeting autophagy/PAI-1 axis may present a novel strategy for repurposing mitoxantrone-based chemotherapy.
Article
Obstetrics & Gynecology
Yukiko Asano, Takayuki Iwaki, Kazuo Umemura, Naohiro Kanayama, Hiroaki Itoh
Summary: The study showed that fibrin had no effect on mouse blastocysts, but significantly suppressed trophoblast growth in human blastocysts. However, trophoblasts in human blastocysts then switched to growth promotion through increased fibrinolysis with urokinase-type plasminogen activator (uPA) activity.
HUMAN REPRODUCTION
(2021)
Article
Biochemistry & Molecular Biology
Claire S. Whyte, Hadj Ahmed. Mostefai, Kim M. Baeten, Andrew J. Lucking, David E. Newby, Nuala A. Booth, Nicola J. Mutch
Summary: The resolution of arterial thrombi relies on the endogenous fibrinolytic system. tPA primarily localizes to the thrombus head in a free and active form. Thrombi formed under high shear conditions are more resistant to fibrinolysis due to less tPA and increased PAI-1 concentrations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Machteld Sillen, Toshio Miyata, Douglas E. Vaughan, Sergei V. Strelkov, Paul J. Declerck
Summary: PAI-1 is a key regulator of the fibrinolytic system, with potential therapeutic significance in various pathological conditions. Small molecule inhibitors like TM5484 may inhibit PAI-1 by binding to the flexible joint region and inducing a substrate to inert form conversion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Esra'a Abudouleh, Fatimah Alhamlan, Arwa A. Al-Qahtani, Marie Fe Bohol, Amal Al Hazzani, Khadija Khorfan, Morad Alkaff, Tarek Owaidah, Ahmed A. Al-Qahtani
Summary: This study investigated coagulation and fibrinolysis parameters in COVID-19 patients and their association with disease severity. The results showed significantly elevated levels of thrombin activatable fibrinolysis inhibitor, fibrinogen, and tissue plasminogen activator in severe patients. Additionally, patients in the ICU had significantly higher levels of plasminogen activator inhibitor-1, tissue plasminogen activator, and thrombin activatable fibrinolysis inhibitor. These coagulation markers can serve as suitable prognostic indicators for hypofibrinolysis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Florence Boissiere-Michot, Caroline Mollevi, Volker Baecker, Evelyne Crapez, William Jacot
Summary: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) have been identified as prognostic and predictive biomarkers in breast cancer, but their clinical use is limited due to the need for fresh-frozen or fresh tumor samples for quantification. This study compared the expression levels of PLAU and SERPINE1 mRNA (corresponding to uPA and PAI-1 proteins) using in situ hybridization with immunometric assay in breast tumor samples. The results showed that in situ hybridization cannot replace the immunometric assay for quantification of uPA and PAI-1 expression.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Article
Hematology
Makiko Yamasaki-Morita, Yasuyuki Arai, Takashi Ishihara, Tomoko Onishi, Hanako Shimo, Kayoko Nakanishi, Yukiko Nishiyama, Tomoyasu Jo, Hidefumi Hiramatsu, Takaya Mitsuyoshi, Chisaki Mizumoto, Junya Kanda, Momoko Nishikori, Toshio Kitawaki, Keiji Nogami, Akifumi Takaori-Kondo, Miki Nagao, Souichi Adachi
Summary: This study analyzed the coagulation/fibrinolysis parameters in DLBCL patients treated with tisagenlecleucel and found a hypofibrinolytic and relatively hypercoagulable state concomitant with elevated PAI-1 levels at the onset of CRS, which gradually resolved after CRS remission. These results contribute to the understanding of CRS-related coagulopathy and highlight the importance of monitoring coagulation/fibrinolysis parameters during CAR-T therapy.
Article
Pharmacology & Pharmacy
Kirstin Meiners, Prisca Hamm, Marcus Gutmann, Jan Niedens, Agnieszka Nowak-Krol, Salvador Pane, Tessa Luehmann
Summary: The study developed three polyethylene glycol (PEG)ylated tPA bioconjugates based on the recombinant human tPA drug Alteplase using site-specific conjugation strategies. These bioconjugates showed improved proteolytic activity, slower inhibition kinetics by PAI-1, and increased hydrodynamic size.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Oncology
Bofang Wang, Baohong Gu, Tao Zhang, Xuemei Li, Na Wang, Chenhui Ma, Lin Xiang, Yunpeng Wang, Lei Gao, Yang Yu, Kewei Song, Puyi He, Yueyan Wang, Jingyu Zhu, Hao Chen
Summary: The fibrinolytic system is involved in various physiological functions and plays a significant role in the pathogenesis of many diseases. Plasminogen activator inhibitor 1 (PAI-1) is a crucial element of this system and acts as an anti-fibrinolytic agent in the normal blood clotting process. PAI-1 is involved in blood diseases, inflammation, obesity, metabolic syndrome, and tumor pathology, exhibiting a paradoxical role in different digestive system tumors.
Article
Obstetrics & Gynecology
Esra Demirel, Reem Sabouni, Neelima Chandra, Ov D. Slayden, David F. Archer
Summary: The study investigates the distribution and concentrations of several receptors and activators within the primate endometrium during artificial menstrual cycles, showing similarities in their expression patterns suggesting overlapping pathways. These findings indicate potential interactions between the plasminogen activator system and steroid receptors in the endometrium.
REPRODUCTIVE SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Colin Berry, Andrew J. Morrow, Mario Marzilli, Carl J. Pepine
Summary: Ischemic heart disease is a leading global health issue, with major subtypes including coronary heart disease and vasomotor disorders. Men are more likely to have coronary heart disease, while women are more likely to have vasomotor disorders. The diagnostic accuracy of tests differs for different subtypes, emphasizing the need for personalized clinical management.
CARDIOVASCULAR DRUGS AND THERAPY
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Davide Cao, Carl J. Pepine, Roxana Mehran
EUROPEAN HEART JOURNAL
(2022)
Article
Public, Environmental & Occupational Health
Scott M. Vouri, Earl J. Morris, Silken A. Usmani, Rachel Reise, Xinyi Jiang, Carl J. Pepine, Todd M. Manini, Daniel C. Malone, Almut G. Winterstein
Summary: The study evaluated the balance between initiation rates of marker drug before and after initiation of an index drug in the absence of prescribing cascades. The results confirmed the prescription sequence symmetry analysis assumption, as loop diuretic initiation rates before and after DH CCB initiation were similar when not influenced by prescribing cascades.
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2022)
Article
Cardiac & Cardiovascular Systems
Ellen C. Keeley, Han J. Li, Christopher R. Cogle, Eileen M. Handberg, C. Noel Bairey Merz, Carl J. Pepine
Summary: This study found that in female patients with CMD, plasma levels of resolvin D1 and maresin 1 were significantly lower, while levels of docosahexaenoic acid and 18-hydroxyeicosapentaenoic acid were significantly higher. This suggests that insufficient or ineffective production of SPM may play a role in the pathophysiology of CMD.
AMERICAN JOURNAL OF CARDIOLOGY
(2022)
Review
Cardiac & Cardiovascular Systems
Elaine M. Richards, Jing Li, Bruce R. Stevens, Carl J. Pepine, Mohan K. Raizada
Summary: Hypertension is a global health problem with significant impacts on morbidity, mortality, and healthcare resource utilization. The prevalence of hypertension is increasing, affecting nearly 50% of American adults. Despite the availability of multiple antihypertensive drugs and lifestyle modifications, blood pressure control remains inadequate in about 1 in 5 hypertensive individuals. This review discusses the hypothesis of the gut-brain axis in hypertension, highlighting the involvement of gut physiology, gut microbiota, and neuroinflammation. The dysfunction of this axis contributes to hypertension through inflammatory mediators, metabolites, gut bacteria, and altered afferent information, leading to neuroinflammation and dysregulated autonomic nervous system activity. Understanding these mechanisms could potentially lead to more effective treatments for hypertension.
CIRCULATION RESEARCH
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Carl J. Pepine, C. Noel Bairey Merz
EUROPEAN HEART JOURNAL
(2023)
Article
Cardiac & Cardiovascular Systems
Steven M. M. Smith, Almut G. G. Winterstein, Matthew J. J. Gurka, Marta G. G. Walsh, Shailina Keshwani, Anne M. M. Libby, William R. R. Hogan, Carl J. J. Pepine, Rhonda M. M. Cooper-DeHoff
Summary: This study reveals significant variation in initial antihypertensive prescribing among new users, highlighting a gap between current guideline recommendations and real-world implementation in early hypertension care.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Letter
Cardiac & Cardiovascular Systems
Judy M. Luu, Pankaj Malhotra, Galen Cook-Wiens, Carl J. Pepine, Eileen M. Handberg, Steven E. Reis, Nathaniel Reichek, Vera Bittner, Janet Wei, Sheryl F. Kelsey, Reddy Sailaja Marpuri, George Sopko, C. Noel Bairey Merz
Article
Public, Environmental & Occupational Health
Scott M. Vouri, Earl J. Morris, Marta Walsh, Jessica Agalliu, Alyssa Dempsey, Leonie Hochleitner, Matthew R. Muschett, Stephan Schmidt, Carl J. Pepine, Steven M. Smith
Summary: This study aimed to comprehensively assess prescribing cascades related to statin medications. The results identified potential prescribing cascades, including laxatives, analgesics, and cephalosporins. These findings are important for reducing the occurrence of prescribing cascades.
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2023)
Article
Cardiac & Cardiovascular Systems
Jing Li, Elaine M. Richards, Ramakumar Tummala, Carl J. Pepine, Mohan K. Raizada, Tao Yang
Summary: Hypertension is associated with gut dysbiosis and altered intestinal immunity. Using sorting techniques and gene sequencing, we found significant differences in IgA(+) and IgA(-) bacteria between hypertensive and normotensive rats. We also identified several IgA-coated bacteria that were negatively correlated with various pathways involved in immune response and epithelium development.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Cardiac & Cardiovascular Systems
David L. DeRemer, Nam K. Nguyen, Avirup Guha, Faraz S. Ahmad, Rhonda M. Cooper-DeHoff, Carl J. Pepine, Michael G. Fradley, Yan Gong
Summary: This study evaluated the differences in cardiac surveillance among different racial and ethnic groups among survivors of cancer after exposure to anthracycline-based treatment. The study found that African American and Hispanic patients had lower participation rates in cardiac surveillance. These results suggest that healthcare providers need to be aware of social inequities and take measures to ensure recommended cardiac surveillance after anthracycline therapy.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Cardiac & Cardiovascular Systems
Teja Chakrala, Roshni Prakash, Carlos Valdes, Carl J. J. Pepine, Ellen C. C. Keeley
Summary: Coronary microvascular dysfunction is often unrecognized but has significant clinical implications. Circulating biomarkers can provide valuable information for the diagnosis and management of this condition, reflecting key pathological processes like inflammation, endothelial dysfunction, oxidative stress, coagulation, and others.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Cardiac & Cardiovascular Systems
Robert F. Hamburger, Yasmeen Taha, Mohammed Ruzieh, James R. Clugston, Eileen M. Handberg, Fred Reifsteck, Matthew W. Martinez, Carl J. Pepine, Katherine M. Edenfield
Summary: This study investigated the effects of intense training on cardiac remodeling in American collegiate football players. The findings showed that training was associated with increases in chamber sizes, left atrial size, and aortic root diameter.
CLINICAL CARDIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Grace Hsin-Min Wang, Earl Morris, Scott M. Vouri, Shailina Keshwani, Stephan Schmidt, Carl J. Pepine, Steven M. Smith
Summary: This study aims to identify modifiable statin characteristics associated with lower risk of prescribing cascades. The results show that compared to low-intensity statins, moderate- or high-intensity statins and the choice of individual statin agents are associated with increased risk of prescribing cascades.
Article
Medicine, General & Internal
Yasmeen K. Taha, Jennifer R. Dungan, Michael T. Weaver, Ke Xu, Eileen M. Handberg, Carl J. Pepine, C. Noel Bairey Merz
Summary: Identifying ischemic heart disease (IHD) in women based on symptoms is challenging, as women are more likely to experience non-cardiac symptoms. More than 50% of women with suspected ischemia have no obstructive coronary disease, leading to impaired outcomes during follow-up. A study aimed to identify symptoms that can predict non-obstructive coronary artery disease (INOCA) in women with clinical evidence of coronary ischemia. The study found that age, left side chest pain, chest discomfort, neck pain, and palpitations had a positive relationship with INOCA, while impending doom and pain in the jaw, left or bilateral arm, and right hand were inversely related to INOCA. The best-fit model accurately predicted INOCA based on age and symptom presentation about 72% of the time.
JOURNAL OF CLINICAL MEDICINE
(2023)