Article
Biochemistry & Molecular Biology
Maria Elena Onore, Marco Savarese, Esther Picillo, Luigia Passamano, Vincenzo Nigro, Luisa Politano
Summary: Mutations in the human desmin gene can cause a range of diseases, including cardiomyopathies and myopathies. Autosomal dominant desminopathies primarily manifest as cardiac conduction disorders, arrhythmias, and cardiomyopathies, while the recessive forms are rare and exhibit variable phenotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Jessica A. Lawrence, Patricia Aguilar-Calvo, Daniel Ojeda-Juarez, Helen Khuu, Katrin Soldau, Donald P. Pizzo, Jin Wang, Adela Malik, Timothy F. Shay, Erin E. Sullivan, Brent Aulston, Seung Min Song, Julia A. Callender, Henry Sanchez, Michael D. Geschwind, Subhojit Roy, Robert A. Rissman, JoAnn Trejo, Nobuyuki Tanaka, Chengbiao Wu, Xu Chen, Gentry N. Patrick, Christina J. Sigurdson
Summary: Endolysosomal defects, including the reduction of Hrs and STAM1, exacerbate synaptic derangements and accelerate neurodegeneration in prion-infected brains. Depletion of neuronal Hrs leads to increased surface levels of PrPC, contributing to the rapidly advancing disease through neurotoxic signaling. The findings highlight the importance of proteostatic pathways and synaptic integrity in prion diseases.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Xuhan Liu, Yuan Liu, Bo Li, Lin Wang, Weihua Zhang
Summary: Desmin myopathy is a rare genetic disorder causing severe atypical cardiomyopathy and skeletal myopathy. Diagnosis is made through genetic testing and supplementary examinations. Early detection and multidisciplinary management are crucial for improving patient outcomes.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Neurosciences
Johan N. K. Larsson, Sofie Nystroem, Per Hammarstrom
Summary: Neurodegenerative diseases are associated with the accumulation of misfolded proteins. HSP10, a molecular chaperone, plays an important role in protein homeostasis in these diseases by influencing fibril formation and structure.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Daniel Soetkamp, Romain Gallet, Sarah J. Parker, Ronald Holewinski, Vidya Venkatraman, Kiel Peck, Joshua Goldhaber, Eduardo Marban, Jennifer E. Van Eyk
Summary: The study suggests that the phosphorylation of sarcomeric proteins is associated with heart failure with preserved ejection fraction, and treatment with cardiosphere-derived cells can partially reverse this process, with PKC beta identified as a potential therapeutic target in HFpEF.
CIRCULATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Aidana Sheryazdanova, Nivea Dias Amoedo, Sara Dufour, Francis Impens, Rodrigue Rossignol, Anna Sablina
Summary: The traditional understanding of aerobic glycolysis in cancer development has been challenged by the discovery of the important role of oxidative phosphorylation (OXPHOS). The study found that the increased expression of OXPHOS proteins in cancer cells is associated with high OXPHOS activity and sensitivity to OXPHOS inhibitors. The ubiquitin hydrolase OTUB1 was identified as a regulator of mitochondrial metabolism essential for lung cancer cell survival.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Cardiac & Cardiovascular Systems
Perry Elliott, Brian M. Drachman, Stephen S. Gottlieb, James E. Hoffman, Scott L. Hummel, Daniel J. Lenihan, Ben Ebede, Balarama Gundapaneni, Benjamin Li, Marla B. Sultan, Sanjiv J. Shah
Summary: This study demonstrates the long-term efficacy of Tafamidis in the treatment of transthyretin amyloid cardiomyopathy, showing that patients who were initially treated with Tafamidis had significantly better survival rates than those who received placebo initially.
CIRCULATION-HEART FAILURE
(2022)
Article
Cardiac & Cardiovascular Systems
Avni Madhani, Natalia Sabogal, Daniel Massillon, Ludwine D. Paul, Carlos Rodriguez, Denise Fine, Stephen Helmke, Morgan Winburn, Damian Kurian, Farbod Raiszadeh, Sergio Teruya, Elizabeth Cohn, Andrew J. Einstein, Edward J. Miller, Lawreen H. Connors, Mathew S. Maurer, Frederick L. Ruberg
Summary: In this study, it was found that 3.4% of self-identified Black individuals carry the V122I variant, and 39% of them exhibit hereditary ATTR-CM. The study also suggests that serum prealbumin concentration may be helpful in diagnosing ATTR-CM in V122I carriers.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Biochemistry & Molecular Biology
Yasuhiro Takenaka, Ikuo Inoue, Masataka Hirasaki, Masaaki Ikeda, Yoshihiko Kakinuma
Summary: We developed a stress-induced premature senescence (SIPS) model in MRC-5 cells and investigated the involvement of mitochondrial function in this model. We found that short-term co-treatment with the complex III inhibitor, antimycin A (AA), attenuated SIPS induced by proteasome inhibitor MG132 or vacuolar-type ATPase inhibitor bafilomycin A1 (BAFA1). AA co-treatment suppressed reactive oxygen species, protein aggregates, and mitochondrial unfolded protein responses (UPRmt), while enhancing mitochondrial biogenesis. These findings highlight the protective effects of temporally inhibiting mitochondrial respiration against premature senescence caused by impaired proteostasis.
Article
Gastroenterology & Hepatology
David A. Rudnick, Jiansheng Huang, Tunda Hidvegi, Andrew S. Chu, Pamela Hale, Admire Munanairi, Dennis J. Dietzen, Paul F. Cliften, Eric Tycksen, Andrew J. Lutkewitte, Brian N. Finck, Stephen C. Pak, Gary A. Silverman, David H. Perlmutter
Summary: Insulin signaling exacerbates hepatic proteotoxicity in PiZ mice with alpha 1-antitrypsin deficiency, and PGC1 alpha is identified as a novel therapeutic target.
Article
Cardiac & Cardiovascular Systems
Yousuf Razvi, Aldostefano Porcari, Concetta Di Nora, Rishi K. K. Patel, Adam Ioannou, Muhammad U. U. Rauf, Ambra Masi, Steven Law, Liza Chacko, Tamer Rezk, Sriram Ravichandran, Janet Gilbertson, Dorota Rowczenio, Iona J. J. Blakeney, Nandita Kaza, David F. F. Hutt, Helen Lachmann, Ashutosh Wechalekar, William Moody, Sern Lim, Colin Chue, Carol Whelan, Lucia Venneri, Ana Martinez-Naharro, Marco Merlo, Gianfranco Sinagra, Ugolino Livi, Philip Hawkins, Marianna Fontana, Julian D. D. Gillmore
Summary: Transthyretin cardiac amyloidosis (ATTR-CM) is a fatal cardiomyopathy. Cardiac transplantation (CT) is a treatment option, but it is considered a contraindication in some centers due to the risk of amyloid recurrence. We reported long-term outcomes of CT in ATTR-CM and found that CT is well-tolerated, improves prognosis, and has a low risk of amyloid recurrence in the cardiac allograft. Survival among the cohort of patients who underwent CT was significantly prolonged compared to UK patients with ATTR-CM generally (p < 0.001).
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Cardiac & Cardiovascular Systems
Bernadet T. Santema, Vicente Artola Arita, Iziah E. Sama, Marielle Kloosterman, Maarten P. van den Berg, Hans L. A. Nienhuis, Isabelle C. Van Gelder, Peter van der Meer, Faiez Zannad, Marco Metra, Jozine M. Ter Maaten, John G. Cleland, Leong L. Ng, Stefan D. Anker, Chim C. Lang, Nilesh J. Samani, Kenneth Dickstein, Gerasimos Filippatos, Dirk J. van Veldhuisen, Carolyn S. P. Lam, Michiel Rienstra, Adriaan A. Voors
Summary: By comparing 92 biomarkers from different pathophysiological domains, the study found 24 biomarkers that were dysregulated in patients with HF and AF. Pathway overrepresentation analyses revealed that AF patients were associated with three pathways related to amyloid-beta, indicating the need for further confirmation in future studies.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Filip Berisha, Konrad R. Goetz, Joerg W. Wegener, Soeren Brandenburg, Hariharan Subramanian, Cristina E. Molina, Andre Ruffer, Johannes Petersen, Alexander Bernhardt, Evaldas Girdauskas, Christiane Jungen, Ulrike Pape, Axel E. Kraft, Svenja Warnke, Diana Lindner, Dirk Westermann, Stefan Blankenberg, Christian Meyer, Gerd Hasenfuss, Stephan E. Lehnart, Viacheslav O. Nikolaev
Summary: This study established a real-time live-cell imaging approach to visualize cAMP levels in the vicinity of cardiac RyR2 in mouse and human failing cardiomyocytes under beta-AR stimulation. The findings revealed a subcellular redistribution of PDEs in cardiac hypertrophy, along with increased beta(2)-AR-dependent RyR2 phosphorylation, sarcoplasmic reticulum calcium leak, and arrhythmia susceptibility in failing mouse and human myocytes. This imaging approach may uncover potential antiarrhythmic targets for heart failure.
CIRCULATION RESEARCH
(2021)
Article
Cell & Tissue Engineering
Guanyi Huang, Anjali Bisaria, Devin L. Wakefield, Tracy M. Yamawaki, Xin Luo, Jingli A. Zhang, Patrick Vigneault, Jinghong Wang, Jeffrey D. Reagan, Oliver Oliverio, Hong Zhou, Chi -Ming Li, Olaia F. Vila, Songli Wang, Fady I. Malik, James J. Hartman, Christopher M. Hale
Summary: In this study, the disease phenotypes of A-band TTNtv-induced dilated cardiomyopathy (DCM) were modeled in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using genome editing and tissue engineering technologies. The study revealed pathogenic proteinopathy, sarcomere defects, aberrant Na+ channel activities, and contractile dysfunction in A-band TTNtv hiPSC-CMs. The findings also demonstrated the potential therapeutic use of sarcomere modulators in reversing DCM disease signatures.
Article
Cardiac & Cardiovascular Systems
Fang Zhu, Frank J. Wolters, Amber Yaqub, Maarten J. G. Leening, Mohsen Ghanbari, Eric Boersma, M. Arfan Ikram, Maryam Kavousi
Summary: This study examined the association of plasma amyloid-13 (A13) with cardiac function and risk of heart failure (HF). The results showed that higher levels of A1340 were associated with worse cardiac function and an increased risk of new onset HF, particularly among men.
JACC-HEART FAILURE
(2023)
Article
Surgery
Clemens Nebert, Christian Mayer, Birgit Zirngast, Lisa Moser, Peter Rainer, Monica D'Orazio, Josef Hermann, Verena Stangl, Heinrich Maechler
Summary: This case report describes drug-induced pericarditis in a patient with rheumatoid arthritis. The exacerbation of pericarditis might be related to the use of etanercept, with underlying rheumatoid arthritis and secondary vasculitis after infection with Staphylococcus aureus also considered as potential triggers.
EUROPEAN SURGERY-ACTA CHIRURGICA AUSTRIACA
(2022)
Review
Genetics & Heredity
Donghwa Kim, Alina Tokmakova, Jung-A A. Woo, Steven S. An, William A. Goddard, Stephen B. Liggett
Summary: GPCRs are a superfamily of receptors activated by a variety of ligands, able to activate different signaling pathways with varying therapeutic effects. Biased ligands may offer new opportunities for drug development by selectively targeting specific pathways, though challenges in understanding structure-function relationships need to be addressed.
MOLECULAR DIAGNOSIS & THERAPY
(2022)
Article
Medicine, General & Internal
Jutta Bergler-Klein, Peter P. Rainer, Markus Wallner, Marc-Michael Zaruba, Jakob Doerler, Armin Boehmer, Tamara Buchacher, Maria Frey, Christopher Adlbrecht, Rupert Bartsch, Mariann Gyoengyoesi, Ursula-Maria Fuerst
Summary: Survival rates in cancer patients are improving due to advancements in oncological treatments. However, the short-term and long-term cardiovascular side effects play a crucial role in the overall outcomes. Cardiotoxicity can manifest as heart failure, treatment-resistant hypertension, acute coronary ischemia, thromboembolism, arrhythmia, and other conditions. Recent recommendations emphasize the importance of assessing baseline cardiac risks and implementing monitoring strategies. Early initiation of cardioprotective therapies and reassessment of cardiac function are recommended if left ventricular ejection fraction or myocardial strain decline during cancer treatment. Collaborative efforts between cardiology and oncology are essential for optimal management of cancer patients.
WIENER KLINISCHE WOCHENSCHRIFT
(2022)
Article
Physiology
Brian T. Deeney, Gaoyuan Cao, Sarah Orfanos, Jordan Lee, Mengyuan Kan, Blanca E. Himes, Vishal Parikh, Cynthia J. Koziol-White, Steven S. An, Reynold A. Panettieri Jr
Summary: Epinephrine plays a role in physiological functions by activating adrenergic receptors in various organs, but its functional role on adrenergic receptors in human bronchial smooth muscle is still not clear. New research has found that human bronchial smooth muscle cells express a high abundance of α1 adrenergic receptor subtype B, and activation of these receptors can induce bronchial smooth muscle cell constriction, potentially leading to asthma attacks. This discovery provides a new basis for reevaluating the role of α1 adrenergic receptor inhibition in asthma treatment.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Critical Care Medicine
Kwangmi Ahn, Raymond B. Penn, Satish Rattan, Reynold A. Panettieri, Benjamin F. Voight, Steven S. An
Summary: Using Mendelian randomization analysis, this study demonstrates causal relationships between gastroesophageal reflux disease (GERD) and atopic disorders (asthma and atopic dermatitis [AD]). Specifically, asthma is shown to be a causal risk factor for AD, and GERD could be a shared pathogenic mechanism for both asthma and AD.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jung-A A. Woo, Maria Castano, Teresa R. Kee, Jordan Lee, Cynthia J. Koziol-White, Steven S. An, Donghwa Kim, David E. Kang, Stephen B. Liggett
Summary: TAS2Rs are bitter taste receptors expressed on human airway smooth muscle (HASM) cells. Activation of TAS2Rs promotes airway relaxation through severing of F-actin. This destabilization of actin is due to cofilin dephosphorylation, which is mediated by TAS2R-induced deactivation of LIM domain kinase. The understanding of this mechanism provides new insights into potential targets for bronchodilators.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Letter
Allergy
En Xu, Gaoyuan Cao, Zhi Yang, Yuanyue Zhang, Youwen Si, Kunal Singh, Joseph Jude, Steven S. An, Cynthia J. Koziol-White, Reynold A. Panettieri, Qi Yang
Article
Biochemistry & Molecular Biology
Eric B. Gebski, Vishal Parikh, Hong Lam, Nicholas Kim, Yury A. Bochkov, Gaoyuan Cao, Reynold A. Panettieri, Richard Kurten, James Gern, Steven S. An, Cynthia J. Koziol-White
Summary: Rhinovirus C15 attenuates agonist-induced bronchodilation, decreases efficacy of current therapeutics, and modulates components of relaxation pathways in airway smooth muscle.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Murilo Delgobo, Emil Weiss, DiyaaElDin, Ashour Leon Richter, Lisa Popiolkowski, Panagiota Arampatzi, Verena Stangl, Paula Arias-Loza, Encarnita Mariotti-Ferrandiz, Peter P. Rainer, Antoine-Emmanuel Saliba, Burkhard Ludewig, Ulrich Hofmann, Stefan Frantz, Gustavo Campos Ramos
Summary: In this study, the researchers investigated how antigen-specific T-helper cells differentiate in the myocardial environment. They used a transgenic T cell receptor model and single-cell transcriptomics to study the cells in the murine infarcted myocardium. The results showed that these cells acquired a regulatory phenotype and influenced tissue repair.
CIRCULATION RESEARCH
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Susanne Sattler, Gustavo Campos Ramos, Burkhard Ludewig, Peter P. Rainer
EUROPEAN HEART JOURNAL
(2023)
Review
Cardiac & Cardiovascular Systems
Mahmoud Abdellatif, Peter P. Rainer, Simon Sedej, Guido Kroemer
Summary: In this Review, Kroemer and colleagues summarize eight molecular hallmarks of cardiovascular ageing, including disabled macroautophagy, loss of proteostasis, genomic instability, epigenetic alterations, mitochondrial dysfunction, cell senescence, dysregulated neurohormonal signalling and inflammation. Targeting these hallmarks therapeutically can attenuate residual cardiovascular risk in older individuals.
NATURE REVIEWS CARDIOLOGY
(2023)
Article
Clinical Neurology
Isra Hatab, Markus Kneihsl, Egbert Bisping, Peter P. Rainer, Simon Fandler-Hoefler, Sebastian Eppinger, Melanie Haidegger, Natalie Berger, Harald Mangge, Reinhold Schmidt, Christian Enzinger, Thomas Gattringer
Summary: This study aimed to compare the predictive value of different clinical routine blood biomarkers on post-stroke mortality over a 5-year follow-up period. The results showed that NT-proBNP is an independent biomarker for predicting death after ischemic stroke, and it is associated with cardioembolic stroke and heart failure.
EUROPEAN STROKE JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Ajay P. Nayak, Elham Javed, Dominic R. Villalba, Yinna Wang, Henry P. Morelli, Sushrut D. Shah, Nicholas Kim, Rennolds S. Ostrom, Reynold A. Panettieri, Steven S. An, Dale D. Tang, Raymond B. Penn
Summary: Prostaglandin E2 has various physiological effects on multiple airway cells through its actions on different E-type prostanoid receptor subtypes. The EP2 and EP4 receptors, in particular, play a role in regulating the contraction and signaling of airway smooth muscle. However, the effectiveness of subtype-specific agonists in relaxing the muscle under different stimulation conditions varies, suggesting the involvement of compartmentalized signaling mechanisms.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Silvia Granata, Donatella Canistro, Fabio Vivarelli, Camilla Morosini, Laura Rullo, Dario Mercatante, Maria Teresa Rodriguez-Estrada, Alessandra Baracca, Gianluca Sgarbi, Giancarlo Solaini, Severino Ghini, Ivan Fagiolino, Stefano Sangiorgi, Moreno Paolini
Summary: The Food and Drug Administration has classified IQOS electronic cigarette as a modified-risk tobacco product. However, IQOS cigarettes still release harmful constituents like conventional cigarettes. A study has shown that IQOS smoking damages liver function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Oncology
Mikaela M. Mallin, Nicholas Kim, Mohammad Ikbal Choudhury, SeJong Lee, Steven S. An, Sean X. Sun, Konstantinos Konstantopoulos, Sarah R. Amend, Kenneth J. Pienta