Article
Cardiac & Cardiovascular Systems
Ryan M. Burke, Ronald A. Dirkx, Pearl Quijada, Janet K. Lighthouse, Amy Mohan, Meghann O'Brien, Wojciech Wojciechowski, Collynn F. Woeller, Richard P. Phipps, Jeffrey D. Alexis, John M. Ashton, Eric M. Small
Summary: Salinomycin as an antifibrotic agent demonstrates potent anti-fibrotic activity in cardiac fibroblasts, prevents cardiac fibrosis and functional decline in mouse models of ischemic and nonischemic heart disease, and inhibits cardiac fibroblast activation by targeting p38/MAPK and Rho signaling. Moreover, salinomycin promotes cardiomyocyte survival and improves coronary vessel density, showing promise for the treatment of heart failure patients.
CIRCULATION RESEARCH
(2021)
Review
Cell Biology
Timoteo Marchini, Lucia Sol Mitre, Dennis Wolf
Summary: Atherosclerosis is a chronic inflammatory disease initiated and maintained by leukocytes, which can lead to myocardial infarction and stroke. Challenges in developing therapies for leukocyte accumulation include the lack of tissue-tropism of targeted factors and unspecific inhibition strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Tianbao Ye, Zhiwen Yan, Cheng Chen, Di Wang, Aiting Wang, Taixi Li, Boshen Yang, Xianting Ding, Chengxing Shen
Summary: This study aimed to investigate the cardioprotective role of lactoferrin (Ltf) in myocardial infarction (MI) and its underlying mechanisms. Proteomic analysis revealed that Ltf was significantly upregulated in MI hearts but decreased in circulation, and its expression was positively correlated with cardiac function. Ltf administration attenuated cardiac fibrosis and remodeling, improved cardiac function, and reduced the incidence of heart failure post-MI.
Article
Chemistry, Multidisciplinary
Xuehui Zheng, Lingxin Liu, Jing Liu, Chen Zhang, Jie Zhang, Yan Qi, Lin Xie, Chunmei Zhang, Guoqing Yao, Peili Bu
Summary: The study shows that adverse remodeling after myocardial infarction (MI) is associated with heart failure and sudden cardiac death. Fibulin7 (FBLN7) is a critical profibrotic regulator of post-MI cardiac remodeling. FBLN7 binds to the epidermal growth factor receptor (EGFR) and induces autophosphorylation of EGFR, leading to fibroblast-to-myofibroblast transdifferentiation and myocardial fibrosis.
Review
Chemistry, Medicinal
Zohreh Varasteh, Wolfgang A. Weber, Christoph Rischpler
Summary: Molecular imaging technologies play a vital role in the detection and treatment of cardiovascular disease, providing unique insights into pathobiological processes and enabling personalized therapy.
Review
Cardiac & Cardiovascular Systems
Ruoshui Li, Nikolaos G. Frangogiannis
Summary: Integrins, a family of surface receptors, play a role in sensing mechanical stress and changes in the matrix environment, and are involved in the regulation of fibrosis. In myocardial fibrosis, integrins are implicated in fibrogenic conversion of cardiac fibroblasts and may mediate recruitment and activation of fibrogenic macrophages. The role of integrins in cardiac fibrosis is dependent on the underlying pathologic condition and further research is needed to fully understand their involvement.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Immunology
Ri-Feng Gao, Xiao Li, Hai-Yan Xiang, Heng Yang, Chun-Yu Lv, Xiao-Lei Sun, Hong-Zhang Chen, Yang Gao, Jue-Sheng Yang, Wei Luo, Yi-Qing Yang, Yan-Hua Tang
Summary: Oridonin, a covalent NLRP3 inhibitor, reduces myocardial fibrosis and preserves cardiac function in a mouse MI model, indicating its potential therapeutic effect on acute MI patients. Additionally, Oridonin decreased the expression levels of inflammatory factors and reduced myocardial macrophage and neutrophil influxes in treated mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qian Yang, Xiao Zong, Lingfang Zhuang, Roubai Pan, Xierenayi Tudi, Qin Fan, Rong Tao
Summary: Adverse cardiac remodeling, including fibrosis, is a major cause of heart failure after myocardial infarction. The enzyme PFKFB3, involved in glucose metabolism, has implications in fibrotic and cardiovascular diseases. In this study, PFKFB3 inhibition using the inhibitor 3PO improved cardiac function and reduced fibrosis in a mouse model of myocardial infarction. PFKFB3 inhibition suppressed the TGF-beta 1/SMAD2/3 signaling pathway and decreased collagen and fibronectin expression, leading to reduced fibrosis. These findings suggest that PFKFB3 inhibition may be a novel therapeutic strategy to reduce chronic heart failure after myocardial infarction.
Article
Cell Biology
Yiteng Liao, Hao Li, Hao Cao, Yun Dong, Lei Gao, Zhongmin Liu, Junbo Ge, Hongming Zhu
Summary: miR-146b-5p is a hypoxia-induced regulator that governs the pro-fibrotic phenotype transition of cardiac cells. Local inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following MI.
Article
Biochemistry & Molecular Biology
Min Zhang, Min Zhang, Ting Zhou, Meilin Liu, Ni Xia, Muyang Gu, Tingting Tang, Shaofang Nie, Zhengfeng Zhu, Bingjie Lv, Jiao Jiao, Xiangping Yang, Xiang Cheng
Summary: ACKR4 plays a critical role in cardiac remodeling post-myocardial infarction by regulating IL-6 production in cardiac fibroblasts and endothelial cell functions to inhibit cardiac fibrosis. Targeting ACKR4 may offer a novel therapeutic strategy for ameliorating cardiac remodeling.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Yong Fu, Jun Shi, Hong Qian, Chaoyi Qin, Lulu Liu, Jiayu Shen, Hao Ma, Lang Ma, Bin Liao, Yingqiang Guo
Summary: This study investigated the therapeutic effect of peritoneal matrix-loaded pirfenidone nanodroplets (NDs) on myocardial infarction (MI) fibrosis. The results showed that the nanodroplets achieved a slow drug release and inhibited cardiac fibroblasts transformation and collagen synthesis. Combining the peritoneal matrix with pirfenidone nanodroplets showed excellent therapeutic effects on fibrosis in MI rats. This study confirmed the feasibility and synergistic effectiveness of the approach and highlighted the potential application of nanomedicine in other biomedical fields.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jan Philipp Schuette, Mailin-Christin Manke, Katherina Hemmen, Patrick Muenzer, Barbara F. Schoerg, Gustavo Campos Ramos, Michaela Pogoda, Valerie Dicenta, Sabrina H. L. Hoffmann, Juergen Pinnecker, Ferdinand Kollotzek, Monika Zdanyte, Karin A. L. Mueller, Yogesh Singh, Andreas F. Mack, Bernd Pichler, Florian Lang, Bernhard Nieswandt, Meinrad Gawaz, Katrin G. Heinze, Nicolas Casadei, Oliver Borst
Summary: Platelet-derived miRNAs play a critical role in myocardial inflammation and structural remodeling in response to myocardial ischemia/reperfusion (I/R). In a mouse model with a Dicer gene deletion, disrupted miRNA processing machinery in platelets led to increased myocardial inflammation, impaired angiogenesis, accelerated cardiac fibrosis, and larger infarct size. These findings highlight the importance of platelet-derived miRNA in regulating cellular processes following myocardial I/R.
CIRCULATION RESEARCH
(2023)
Review
Cell Biology
Akihiko Kubota, Nikolaos G. Frangogiannis
Summary: Following myocardial infarction, macrophages play important roles in both injurious and reparative responses. They regulate the inflammatory response through phagocytosis and secretion of mediators, and contribute to the repair of the infarcted heart. However, the relationship between transcriptomic profiles and functional properties of macrophages in infarcted hearts is still unclear.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Engineering, Biomedical
Yanxin Zhang, Xin Li, Zhaowenbin Zhang, Huili Li, Dongmin Chen, Yiren Jiao, Chen Fan, Zhen Zeng, Jiang Chang, Yuhong Xu, Baowei Peng, Chen Yang, Yumei Que
Summary: This study developed a Zn2SiO4 bioceramic that can release bioactive SiO32- and Zn2+ ions simultaneously, which have synergistic effects on promoting endothelial cell angiogenesis, inhibiting cardiomyocyte apoptosis, and protecting myocardial mitochondria against reactive oxygen species-induced injury. In vivo outcomes from a murine MI model demonstrated that systemic administration or local application of the Zn2SiO4 extract or composite hydrogel promoted cardiac function and reduced cardiac fibrosis, aiding myocardial repair.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cardiac & Cardiovascular Systems
Mei Yang, Jun Xiong, Qiang Zou, Xi Wang, Ke Hu, Qingyan Zhao
Summary: The results of this study demonstrated that sinapic acid attenuated structural and neural remodeling by promoting macrophage M2 polarization via PPAR gamma activation after myocardial infarction.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Nikolaos G. Frangogiannis
TRENDS IN CARDIOVASCULAR MEDICINE
(2020)
Review
Immunology
Nikolaos G. Frangogiannis
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Review
Cardiac & Cardiovascular Systems
Anis Hanna, Nikolaos G. Frangogiannis
CARDIOVASCULAR DRUGS AND THERAPY
(2020)
Editorial Material
Cardiac & Cardiovascular Systems
Nikolaos G. Frangogiannis
EUROPEAN HEART JOURNAL
(2020)
Review
Cardiac & Cardiovascular Systems
Nikolaos G. Frangogiannis
Summary: Transforming growth factor-beta (TGF beta) plays an important role in myocardial diseases, regulating the phenotype and function of cardiovascular cells, participating in cardiac repair and remodeling.
NATURE REVIEWS CARDIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Linda Alex, Izabela Tuleta, Venugopal Harikrishnan, Nikolaos G. Frangogiannis
Summary: Pericytes and fibroblasts in the myocardium are distinct populations of cardiac interstitial cells, with different transcriptional signatures. The inducible NG2(CreER) driver is optimal for targeting cardiac pericytes, while the inducible PDGFR beta(CreER) line lacks specificity.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Pharmacology & Pharmacy
Claudio Humeres, Harikrishnan Venugopal, Nikolaos G. Frangogiannis
Summary: In the infarcted and failing hearts, TGF-beta superfamily members regulate inflammatory, reparative, fibrogenic, and hypertrophic responses through activation of Smad-dependent and Smad-independent cascades. The different Smad pathways have diverse roles in different cell types, playing important roles in the repair and remodeling of the heart. Understanding the regulation of Smad pathways may provide new therapeutic strategies for myocardial infarction and heart failure.
CURRENT OPINION IN PHARMACOLOGY
(2022)
Review
Cell Biology
Harikrishnan Venugopal, Anis Hanna, Claudio Humeres, Nikolaos G. Frangogiannis
Summary: This review discusses the mechanisms, roles, and fate of fibroblasts in the infarcted heart. Following a myocardial infarction, fibroblasts undergo phenotypic transitions and contribute to inflammatory, reparative, and angiogenic responses. They form collagen-based scars to protect the infarcted ventricle and may also stimulate angiogenesis. Prolonged activation of fibroblasts may contribute to adverse remodeling and heart failure.
Article
Biochemistry & Molecular Biology
Jun Li, Ruoshui Li, Izabela Tuleta, Silvia C. Hernandez, Claudio Humeres, Anis Hanna, Bijun Chen, Nikolaos G. Frangogiannis
Summary: The role of macrophage Smad7 in regulating inflammation and repair after myocardial infarction is limited. The anti-inflammatory effects of TGF-beta in macrophages are not restrained by endogenous Smad7 induction.
Review
Cell Biology
Akihiko Kubota, Nikolaos G. Frangogiannis
Summary: Following myocardial infarction, macrophages play important roles in both injurious and reparative responses. They regulate the inflammatory response through phagocytosis and secretion of mediators, and contribute to the repair of the infarcted heart. However, the relationship between transcriptomic profiles and functional properties of macrophages in infarcted hearts is still unclear.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Linda Alex, Izabela Tuleta, Anis Hanna, Nikolaos G. Frangogiannis
Summary: Interstitial and perivascular fibrosis may contribute to diabetes-associated heart failure. Pericyte to fibroblast conversion is not the main mechanism of diabetic fibrosis, but a matrix-preserving fibroblast program is involved, which is independent of myofibroblast conversion and only partially explained by the hyperglycemic environment.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Nikolaos G. Frangogiannis
CARDIOVASCULAR RESEARCH
(2023)
Article
Medicine, Research & Experimental
Claudio Humeres, Arti V. Shinde, Anis Hanna, Linda Alex, Silvia C. Hernandez, Ruoshui Li, Bijun Chen, Simon J. Conway, Nikolaos G. Frangogiannis
Summary: Repair of the infarcted heart requires TGF-beta/Smad3 signaling in cardiac myofibroblasts, but it needs to be tightly regulated to prevent excessive fibrosis and adverse remodeling.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Anis Hanna, Arti V. Shinde, Ruoshui Li, Linda Alex, Claudio Humeres, Prasanth Balasubramanian, Nikolaos G. Frangogiannis
Summary: Tissue injury leads to alterations in collagen network, with specific patterns of collagen denaturation observed during different phases of infarct healing. MT1-MMP plays a significant role in pericellular collagen denaturation, while mechanical tension can induce peripheral collagen denaturation. Chronic collagen denaturation may contribute to post-infarction heart failure.
Review
Cardiac & Cardiovascular Systems
Nikolaos G. Frangogiannis
Summary: Myocardial fibrosis, characterized by the expansion of cardiac interstitium through deposition of extracellular matrix proteins, is a common pathophysiologic feature in various myocardial conditions. Activated fibroblasts and myofibroblasts play a central role in cardiac fibrosis, producing matrix proteins and triggering fibrogenic signalling cascades in response to stress. Immune cells, vascular cells, and cardiomyocytes can also contribute to fibrosis, while fibrotic changes may disrupt cardiac function and play a role in arrhythmogenesis.
CARDIOVASCULAR RESEARCH
(2021)