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3. Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis

Author

Zheng, Kang H, Tsimikas, Sotirios, Pawade, Tania, Kroon, Jeffrey, Jenkins, William SA, Doris, Mhairi K, White, Audrey C, Timmers, Nyanza KLM, Hjortnaes, Jesper, Rogers, Maximillian A, Aikawa, Elena, Arsenault, Benoit J, Witztum, Joseph L, Newby, David E, Koschinsky, Marlys L, Fayad, Zahi A, Stroes, Erik SG, Boekholdt, S Matthijs, and Dweck, Marc R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Biomedical Imaging, Cardiovascular, Heart Disease, Age Factors, Aged, Aged, 80 and over, Aortic Valve, Aortic Valve Stenosis, Apolipoprotein B-100, Biomarkers, Calcinosis, Cohort Studies, Disease Progression, Echocardiography, Doppler, Female, Humans, Hyperlipidemias, Lipoprotein(a), Male, Middle Aged, Phospholipids, Positron-Emission Tomography, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Sex Factors, Survival Analysis, Tomography, X-Ray Computed, aortic valve stenosis, calcific aortic valve disease, lipoprotein(a), oxidized phospholipids, valvular interstitial cells, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundLipoprotein(a) [Lp(a)], a major carrier of oxidized phospholipids (OxPL), is associated with an increased incidence of aortic stenosis (AS). However, it remains unclear whether elevated Lp(a) and OxPL drive disease progression and are therefore targets for therapeutic intervention.ObjectivesThis study investigated whether Lp(a) and OxPL on apolipoprotein B-100 (OxPL-apoB) levels are associated with disease activity, disease progression, and clinical events in AS patients, along with the mechanisms underlying any associations.MethodsThis study combined 2 prospective cohorts and measured Lp(a) and OxPL-apoB levels in patients with AS (Vmax >2.0 m/s), who underwent baseline 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), repeat computed tomography calcium scoring, and repeat echocardiography. In vitro studies investigated the effects of Lp(a) and OxPL on valvular interstitial cells.ResultsOverall, 145 patients were studied (68% men; age 70.3 ± 9.9 years). On baseline positron emission tomography, patients in the top Lp(a) tertile had increased valve calcification activity compared with those in lower tertiles (n = 79; 18F-NaF tissue-to-background ratio of the most diseased segment: 2.16 vs. 1.97; p = 0.043). During follow-up, patients in the top Lp(a) tertile had increased progression of valvular computed tomography calcium score (n = 51; 309 AU/year [interquartile range: 142 to 483 AU/year] vs. 93 AU/year [interquartile range: 56 to 296 AU/year; p = 0.015), faster hemodynamic progression on echocardiography (n = 129; 0.23 ± 0.20 m/s/year vs. 0.14 ± 0.20 m/s/year] p = 0.019), and increased risk for aortic valve replacement and death (n = 145; hazard ratio: 1.87; 95% CI: 1.13 to 3.08; p = 0.014), compared with lower tertiles. Similar results were noted with OxPL-apoB. In vitro, Lp(a) induced osteogenic differentiation of valvular interstitial cells, mediated by OxPL and inhibited with the E06 monoclonal antibody against OxPL.ConclusionsIn patients with AS, Lp(a) and OxPL drive valve calcification and disease progression. These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis.

Published
2019

5. Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays

Author

Clift, Cassandra L., primary, Blaser, Mark C., additional, Gerrits, Willem, additional, Turner, Mandy E., additional, Sonawane, Abhijeet, additional, Pham, Tan, additional, Andresen, Jason L., additional, Fenton, Owen S., additional, Grolman, Joshua M., additional, Campedelli, Alesandra, additional, Buffolo, Fabrizio, additional, Schoen, Frederick J., additional, Hjortnaes, Jesper, additional, Muehlschlegel, Jochen D., additional, Mooney, David J., additional, Aikawa, Masanori, additional, Singh, Sasha A., additional, Langer, Robert, additional, and Aikawa, Elena, additional

Published
2024
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6. Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays

Author

CTC, Regenerative Medicine and Stem Cells, Clift, Cassandra L., Blaser, Mark C., Gerrits, Willem, Turner, Mandy E., Sonawane, Abhijeet, Pham, Tan, Andresen, Jason L., Fenton, Owen S., Grolman, Joshua M., Campedelli, Alesandra, Buffolo, Fabrizio, Schoen, Frederick J., Hjortnaes, Jesper, Muehlschlegel, Jochen D., Mooney, David J., Aikawa, Masanori, Singh, Sasha A., Langer, Robert, Aikawa, Elena, CTC, Regenerative Medicine and Stem Cells, Clift, Cassandra L., Blaser, Mark C., Gerrits, Willem, Turner, Mandy E., Sonawane, Abhijeet, Pham, Tan, Andresen, Jason L., Fenton, Owen S., Grolman, Joshua M., Campedelli, Alesandra, Buffolo, Fabrizio, Schoen, Frederick J., Hjortnaes, Jesper, Muehlschlegel, Jochen D., Mooney, David J., Aikawa, Masanori, Singh, Sasha A., Langer, Robert, and Aikawa, Elena

Published
2024

7. Tri-layered elastomeric scaffolds for engineering heart valve leaflets

Author

Masoumi, Nafiseh, Annabi, Nasim, Assmann, Alexander, Larson, Benjamin L, Hjortnaes, Jesper, Alemdar, Neslihan, Kharaziha, Mahshid, Manning, Keefe B, Mayer, John E, and Khademhosseini, Ali

Subjects
Biotechnology, Regenerative Medicine, Stem Cell Research - Nonembryonic - Non-Human, Bioengineering, Cardiovascular, Stem Cell Research, Transplantation, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Musculoskeletal, Animals, Anisotropy, Aortic Valve, Elastomers, Heart Valve Prosthesis, Humans, In Vitro Techniques, Materials Testing, Microscopy, Electron, Scanning, Polymers, Pulmonary Valve, Sheep, Tissue Engineering, Tissue Scaffolds, Microfabricated elastomer, Electrospinning, Biodegradable scaffold, Anisotropic mechanical properties, Heart valve tissue engineering
Abstract

Tissue engineered heart valves (TEHVs) that can grow and remodel have the potential to serve as permanent replacements of the current non-viable prosthetic valves particularly for pediatric patients. A major challenge in designing functional TEHVs is to mimic both structural and anisotropic mechanical characteristics of the native valve leaflets. To establish a more biomimetic model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning and microfabrication techniques. These constructs were fabricated by assembling microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone) (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic mechanical properties similar to the mechanical characteristics of the native heart valves. The engineered scaffolds supported the growth of valvular interstitial cells (VICs) and mesenchymal stem cells (MSCs) within the 3D structure and promoted the deposition of heart valve extracellular matrix (ECM). MSCs were also organized and aligned along the anisotropic axes of the engineered tri-layered scaffolds. In addition, the fabricated constructs opened and closed properly in an ex vivo model of porcine heart valve leaflet tissue replacement. The engineered tri-layered scaffolds have the potential for successful translation towards TEHV replacements.

Published
2014

8. How microsimulation translates outcome estimates to patient lifetime event occurrence in the setting of heart valve disease.

Author

Notenboom, Maximiliaan L, Rhellab, Reda, Etnel, Jonathan R G, Huygens, Simone A, Hjortnaes, Jesper, Kluin, Jolanda, Takkenberg, Johanna J M, and Veen, Kevin M

Subjects
HEART valve diseases, CARDIAC patients
Abstract

Open in new tab Download slide Treatment decisions in healthcare often carry lifelong consequences that can be challenging to foresee. As such, tools that visualize and estimate outcome after different lifetime treatment strategies are lacking and urgently needed to support clinical decision-making in the setting of rapidly evolving healthcare systems, with increasingly numerous potential treatments. In this regard, microsimulation models may prove to be valuable additions to current risk-prediction models. Notable advantages of microsimulation encompass input from multiple data sources, the ability to move beyond time-to-first-event analysis, accounting for multiple types of events and generating projections of lifelong outcomes. This review aims to clarify the concept of microsimulation, also known as individualized state-transition models, and help clinicians better understand its potential in clinical decision-making. A practical example of a patient with heart valve disease is used to illustrate key components of microsimulation models, such as health states, transition probabilities, input parameters (e.g. evidence-based risks of events) and various aspects of mortality. Finally, this review focuses on future efforts needed in microsimulation to allow for increasing patient-tailoring of the models by extending the general structure with patient-specific prediction models and translating them to meaningful, user-friendly tools that may be used by both clinician and patient to support clinical decision-making. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Intracellular Proteomics and Extracellular Vesiculomics as a Metric of Disease Recapitulation in 3D Bioprinted Aortic Valve Arrays

Author

Clift, Cassandra L., primary, Blaser, Mark C., additional, Gerrits, Willem, additional, Turner, Mandy E., additional, Sonawane, Abhijeet R., additional, Pham, Tan, additional, Andresen, Jason L., additional, Fenton, Owen S., additional, Grolman, Joshua M., additional, Buffolo, Fabrizio, additional, Schoen, Frederick J., additional, Hjortnaes, Jesper, additional, Muehlschlegel, Jochen D., additional, Mooney, David J., additional, Aikawa, Masanori, additional, Singh, Sasha A., additional, Langer, Robert, additional, and Aikawa, Elena, additional

Published
2023
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12. Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation

Author

Nyns, Emile C.A. (author), Portero, Vincent (author), Deng, Shanliang (author), Jin, T. (author), Harlaar, Niels (author), Bart, Cindy I. (author), van Brakel, Thomas J. (author), Palmen, Meindert (author), Hjortnaes, Jesper (author), Ramkisoensing, Arti A. (author), Zhang, Kouchi (author), Poelma, René H. (author), Ördög, Balázs (author), de Vries, Antoine A.F. (author), Pijnappels, Daniël A. (author), Nyns, Emile C.A. (author), Portero, Vincent (author), Deng, Shanliang (author), Jin, T. (author), Harlaar, Niels (author), Bart, Cindy I. (author), van Brakel, Thomas J. (author), Palmen, Meindert (author), Hjortnaes, Jesper (author), Ramkisoensing, Arti A. (author), Zhang, Kouchi (author), Poelma, René H. (author), Ördög, Balázs (author), de Vries, Antoine A.F. (author), and Pijnappels, Daniël A. (author)

Abstract

Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. Methods: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue. Results: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565-nm light pulses at an intensity of 25 mW/mm2 achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4). Conclusion: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration., Electronic Components, Technology and Materials

Published
2023
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13. Cyclic strain has antifibrotic effects on the human cardiac fibroblast transcriptome in a human cardiac fibrosis-on-a-chip platform

Author

Arts Assistenten CTC, Research UMC Utrecht, Experimental Cardiology Laboratory, Onderzoek Precision medicine, Onderzoek Cardiovasculair Reg. Med., Circulatory Health, Regenerative Medicine and Stem Cells, CTC, Onderzoek CTC, Bracco Gartner, Tom C.L., Wang, Ye, Leiteris, Laurynas, van Adrichem, Iris, Marsman, Judith, Goumans, Marie José, Bouten, Carlijn V.C., Sluijter, Joost P.G., den Toonder, Jaap M.J., Suyker, Willem J.L., Hjortnaes, Jesper, Arts Assistenten CTC, Research UMC Utrecht, Experimental Cardiology Laboratory, Onderzoek Precision medicine, Onderzoek Cardiovasculair Reg. Med., Circulatory Health, Regenerative Medicine and Stem Cells, CTC, Onderzoek CTC, Bracco Gartner, Tom C.L., Wang, Ye, Leiteris, Laurynas, van Adrichem, Iris, Marsman, Judith, Goumans, Marie José, Bouten, Carlijn V.C., Sluijter, Joost P.G., den Toonder, Jaap M.J., Suyker, Willem J.L., and Hjortnaes, Jesper

Published
2023

16. Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation.

Author

Nyns, Emile C. A., Portero, Vincent, Deng, Shanliang, Jin, Tianyi, Harlaar, Niels, Bart, Cindy I., van Brakel, Thomas J., Palmen, Meindert, Hjortnaes, Jesper, Ramkisoensing, Arti A., Zhang, Guo Qi, Poelma, René H., Ördög, Balázs, de Vries, Antoine A. F., and Pijnappels, Daniël A.

Subjects
ATRIAL fibrillation, ELECTRIC countershock, RATS, ION channels, PHOTOMETRY
Abstract

Background: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. Objective: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. Methods: Atria of adult and aged rats were optogenetically modified to express light‐gated ion channels (i.e., red‐activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue. Results: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565‐nm light pulses at an intensity of 25 mW/mm2 achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4). Conclusion: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration. [ABSTRACT FROM AUTHOR]

Published
2023
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19. The Aortic Root in Acute Type A Dissection: Repair or Replace?

Author

Arabkhani, Bardia, Verhoef, Jos, Tomšič, Anton, van Brakel, Thomas J., Hjortnaes, Jesper, and Klautz, Robert J.M.

Abstract

The effect of an "aggressive" approach on the aortic root in acute type A aortic dissection (ATAAD) remains insufficiently explored. Retrospective analysis was conducted between 1992 and 2020 of a single-center, prospective cohort of consecutive patients aged ≥18 years diagnosed with ATAAD. Patients were divided into 2 groups: aortic root replacement (ARR; prosthetic or valve-sparing root replacement, n = 141) and conservative root approach (CRA; root sparing of partially dissected root, n = 90; and supracoronary ascending replacement in nondissected root, n = 68). Inverse probability weighting was used to compare patients with different preoperative characteristics. Mean follow-up was 5.1 (0-21) years in ARR and 7.1 (0-25) years in CRA. The frequency of ARR increased over the years, with 19% and 78% of patients undergoing ARR in the earliest and most recent periods, respectively. Early mortality decreased over the years, despite a more aggressive approach, and remained lower in ARR. CRA was associated with a higher hazard of late mortality (hazard ratio, 1.38; 95% CI, 1.12-1.68; P =.001) and reintervention (hazard ratio, 2.08; 95% CI, 1.44-3.56; P =.001). After CRA, new-onset aortic valve insufficiency was a common cause of reintervention. Over the years, there was a gradual increase in the root replacement approach in ATAAD. Root replacement was associated with better long-term survival and fewer reinterventions compared with the conservative approach, whereas the in-hospital mortality decreased during these years. Hence, aggressive root replacement is safe and may be applied in ATAAD with good long-term clinical results, without increased hospital mortality. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Pirfenidone Has Anti-fibrotic Effects in a Tissue-Engineered Model of Human Cardiac Fibrosis

Author

Arts Assistenten CTC, Pathologie Bachelor Research hub, Team Onderzoek, Circulatory Health, Regenerative Medicine and Stem Cells, Team Medisch, CTC, Onderzoek Cardiovasculair Reg. Med., Onderzoek CTC, Bracco Gartner, Tom, Crnko, S, Leiteris, Laurynas, van Adrichem, Iris, van Laake, Linda W., Bouten, Carlijn V. C., Goumans, Marie-Jose, Suyker, Willem, Sluijter, Joost P.G., Hjortnaes, Jesper, Arts Assistenten CTC, Pathologie Bachelor Research hub, Team Onderzoek, Circulatory Health, Regenerative Medicine and Stem Cells, Team Medisch, CTC, Onderzoek Cardiovasculair Reg. Med., Onderzoek CTC, Bracco Gartner, Tom, Crnko, S, Leiteris, Laurynas, van Adrichem, Iris, van Laake, Linda W., Bouten, Carlijn V. C., Goumans, Marie-Jose, Suyker, Willem, Sluijter, Joost P.G., and Hjortnaes, Jesper

Published
2022

24. Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes

Author

Onderzoek Cardiovasculair Reg. Med., Onderzoek Precision medicine, Pathologie Groep Bovenschen, Infection & Immunity, Cancer, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Yuan, Qianliang, Maas, Renee G.C., Brouwer, Ellen C.J., Pei, Jiayi, Blok, Christian Snijders, Popovic, Marko A., Paauw, Nanne J., Bovenschen, Niels, Hjortnaes, Jesper, Harakalova, Magdalena, Doevendans, Pieter A., Sluijter, Joost P.G., van der Velden, Jolanda, Buikema, Jan W., Onderzoek Cardiovasculair Reg. Med., Onderzoek Precision medicine, Pathologie Groep Bovenschen, Infection & Immunity, Cancer, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Yuan, Qianliang, Maas, Renee G.C., Brouwer, Ellen C.J., Pei, Jiayi, Blok, Christian Snijders, Popovic, Marko A., Paauw, Nanne J., Bovenschen, Niels, Hjortnaes, Jesper, Harakalova, Magdalena, Doevendans, Pieter A., Sluijter, Joost P.G., van der Velden, Jolanda, and Buikema, Jan W.

Published
2022

27. Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes

Author

Yuan, Qianliang, primary, Maas, Renee G. C., additional, Brouwer, Ellen C. J., additional, Pei, Jiayi, additional, Blok, Christian Snijders, additional, Popovic, Marko A., additional, Paauw, Nanne J., additional, Bovenschen, Niels, additional, Hjortnaes, Jesper, additional, Harakalova, Magdalena, additional, Doevendans, Pieter A., additional, Sluijter, Joost P. G., additional, van der Velden, Jolanda, additional, and Buikema, Jan W., additional

Published
2022
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32. Radiation Induces Valvular Interstitial Cell Calcific Response in an in vitro Model of Calcific Aortic Valve Disease

Author

Meerman, Manon, Driessen, Rob, van Engeland, Nicole C.A., Bergsma, Irith, Steenhuijsen, Jacco L.G., Kozono, David, Aikawa, Elena, Hjortnaes, Jesper, Bouten, Carlijn V.C., Meerman, Manon, Driessen, Rob, van Engeland, Nicole C.A., Bergsma, Irith, Steenhuijsen, Jacco L.G., Kozono, David, Aikawa, Elena, Hjortnaes, Jesper, and Bouten, Carlijn V.C.

Abstract

Background: Mediastinal ionizing radiotherapy is associated with an increased risk of valvular disease, which demonstrates pathological hallmarks similar to calcific aortic valve disease (CAVD). Despite advances in radiotherapy techniques, the prevalence of comorbidities such as radiation-associated valvular disease is still increasing due to improved survival of patients receiving radiotherapy. However, the mechanisms of radiation-associated valvular disease are largely unknown. CAVD is considered to be an actively regulated disease process, mainly controlled by valvular interstitial cells (VICs). We hypothesize that radiation exposure catalyzes the calcific response of VICs and, therefore, contributes to the development of radiation-associated valvular disease. Methods and Results: To delineate the relationship between radiation and VIC behavior (morphology, calcification, and matrix turnover), two different in vitro models were established: (1) VICs were cultured two-dimensional (2D) on coverslips in control medium (CM) or osteogenic medium (OM) and irradiated with 0, 2, 4, 8, or 16 Gray (Gy); and (2) three-dimensional (3D) hydrogel system was designed, loaded with VICs and exposed to 0, 4, or 16 Gy of radiation. In both models, a dose-dependent decrease in cell viability and proliferation was observed in CM and OM. Radiation exposure caused myofibroblast-like morphological changes and differentiation of VICs, as characterized by decreased αSMA expression. Calcification, as defined by increased alkaline phosphatase activity, was mostly present in the 2D irradiated VICs exposed to 4 Gy, while after exposure to higher doses VICs acquired a unique giant fibroblast-like cell morphology. Finally, matrix turnover was significantly affected by radiation exposure in the 3D irradiated VICs, as shown by decreased collagen staining and increased MMP-2 and MMP-9 activity. Conclusions: The presented work demonstrates that radiation exposure enhances the calcific response i

Published
2021

33. Advanced in vitro modeling to study the paradox of mechanically induced cardiac fibrosis

Author

Bracco Gartner, Tom, Stein, Jeroen, Muylaert, Dimitri, Bouten, Carlijn, Doevendans, Pieter, Khademhosseini, Ali, Suyker, Willem, Sluijter, Joost, Hjortnaes, Jesper, Bracco Gartner, Tom, Stein, Jeroen, Muylaert, Dimitri, Bouten, Carlijn, Doevendans, Pieter, Khademhosseini, Ali, Suyker, Willem, Sluijter, Joost, and Hjortnaes, Jesper

Abstract

In heart failure, cardiac fibrosis is the result of an adverse remodeling process. Collagen is continuously synthesized in the myocardium in an ongoing attempt of the heart to repair itself. The resulting collagen depositions act counterproductively, causing diastolic dysfunction and disturbing electrical conduction. Efforts to treat cardiac fibrosis specifically have not been successful and the molecular etiology is only partially understood. The differentiation of quiescent cardiac fibroblasts to extracellular matrix-depositing myofibroblasts is a hallmark of cardiac fibrosis and a key aspect of the adverse remodeling process. This conversion is induced by a complex interplay of biochemical signals and mechanical stimuli. Tissue engineered 3D-models to study cardiac fibroblast behavior in vitro indicate that cyclic strain can activate a myofibroblast-phenotype. This raises the question how fibroblast quiescence is maintained in the healthy myocardium, despite continuous stimulation of ultimately pro-fibrotic mechanotransductive pathways. In this review, we will discuss the convergence of biochemical and mechanical differentiation signals of myofibroblasts, and hypothesize how these affect this paradoxical quiescence.

Published
2021

35. Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel

Author

Circulatory Health, Experimentele Afd. Cardiologie 2, Onderzoek CTC, Regenerative Medicine and Stem Cells, Team Medisch, Onderzoek Cardiovasculair Reg. Med., van der Ven, Casper F T, Tibbitt, Mark W, Conde, João, van Mil, Alain, Hjortnaes, Jesper, Doevendans, Pieter A, Sluijter, Joost P G, Aikawa, Elena, Langer, Robert S, Circulatory Health, Experimentele Afd. Cardiologie 2, Onderzoek CTC, Regenerative Medicine and Stem Cells, Team Medisch, Onderzoek Cardiovasculair Reg. Med., van der Ven, Casper F T, Tibbitt, Mark W, Conde, João, van Mil, Alain, Hjortnaes, Jesper, Doevendans, Pieter A, Sluijter, Joost P G, Aikawa, Elena, and Langer, Robert S

Published
2021

36. Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes

Author

Experimentele Afd. Cardiologie 2, Onderzoek Precision medicine, Circulatory Health, Perfusie, Onderzoek CTC, Regenerative Medicine and Stem Cells, Team Medisch, Onderzoek Cardiovasculair Reg. Med., Maas, Renee G.C., Lee, Soah, Harakalova, Magdalena, Snijders Blok, Christian J.B., Goodyer, William R., Hjortnaes, Jesper, Doevendans, Pieter A.F.M., Van Laake, Linda W., van der Velden, Jolanda, Asselbergs, Folkert W., Wu, Joseph C., Sluijter, Joost P.G., Wu, Sean M., Buikema, Jan W., Experimentele Afd. Cardiologie 2, Onderzoek Precision medicine, Circulatory Health, Perfusie, Onderzoek CTC, Regenerative Medicine and Stem Cells, Team Medisch, Onderzoek Cardiovasculair Reg. Med., Maas, Renee G.C., Lee, Soah, Harakalova, Magdalena, Snijders Blok, Christian J.B., Goodyer, William R., Hjortnaes, Jesper, Doevendans, Pieter A.F.M., Van Laake, Linda W., van der Velden, Jolanda, Asselbergs, Folkert W., Wu, Joseph C., Sluijter, Joost P.G., Wu, Sean M., and Buikema, Jan W.

Published
2021

37. Myocardial Disease and Long-Distance Space Travel: Solving the Radiation Problem

Author

Arts Assistenten CTC, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, CTC, Onderzoek CTC, Meerman, Manon, Bracco Gartner, Tom C L, Buikema, Jan Willem, Wu, Sean M, Siddiqi, Sailay, Bouten, Carlijn V C, Grande-Allen, K Jane, Suyker, Willem J L, Hjortnaes, Jesper, Arts Assistenten CTC, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, CTC, Onderzoek CTC, Meerman, Manon, Bracco Gartner, Tom C L, Buikema, Jan Willem, Wu, Sean M, Siddiqi, Sailay, Bouten, Carlijn V C, Grande-Allen, K Jane, Suyker, Willem J L, and Hjortnaes, Jesper

Published
2021

38. Advanced in Vitro Modeling to Study the Paradox of Mechanically Induced Cardiac Fibrosis

Author

Arts Assistenten CTC, Nefro Vasculaire Geneeskunde, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, CTC, Onderzoek Cardiovasculair Reg. Med., Onderzoek CTC, Bracco Gartner, Thomas C.L., Stein, Jeroen M., Muylaert, Dimitri E.P., Bouten, Carlijn V.C., Doevendans, Pieter A., Khademhosseini, Ali, Suyker, Willem J.L., Sluijter, Joost P.G., Hjortnaes, Jesper, Arts Assistenten CTC, Nefro Vasculaire Geneeskunde, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, CTC, Onderzoek Cardiovasculair Reg. Med., Onderzoek CTC, Bracco Gartner, Thomas C.L., Stein, Jeroen M., Muylaert, Dimitri E.P., Bouten, Carlijn V.C., Doevendans, Pieter A., Khademhosseini, Ali, Suyker, Willem J.L., Sluijter, Joost P.G., and Hjortnaes, Jesper

Published
2021

40. Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes

Author

Maas, Renee G.C., primary, Lee, Soah, additional, Harakalova, Magdalena, additional, Snijders Blok, Christian J.B., additional, Goodyer, William R., additional, Hjortnaes, Jesper, additional, Doevendans, Pieter A.F.M., additional, Van Laake, Linda W., additional, van der Velden, Jolanda, additional, Asselbergs, Folkert W., additional, Wu, Joseph C., additional, Sluijter, Joost P.G., additional, Wu, Sean M., additional, and Buikema, Jan W., additional

Published
2021
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41. Integrative Multi-Omics Analysis in Calcific Aortic Valve Disease Reveals a Link to the Formation of Amyloid-Like Deposits

Author

Onderzoek CTC, Regenerative Medicine and Stem Cells, Arts Assistenten CTC, Heuschkel, Marina A, Skenteris, Nikolaos T, Hutcheson, Joshua D, van der Valk, Dewy D, Bremer, Juliane, Goody, Philip, Hjortnaes, Jesper, Jansen, Felix, Bouten, Carlijn V C, van den Bogaerdt, Antoon, Matic, Ljubica, Marx, Nikolaus, Goettsch, Claudia, Onderzoek CTC, Regenerative Medicine and Stem Cells, Arts Assistenten CTC, Heuschkel, Marina A, Skenteris, Nikolaos T, Hutcheson, Joshua D, van der Valk, Dewy D, Bremer, Juliane, Goody, Philip, Hjortnaes, Jesper, Jansen, Felix, Bouten, Carlijn V C, van den Bogaerdt, Antoon, Matic, Ljubica, Marx, Nikolaus, and Goettsch, Claudia

Published
2020

42. The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease : a cohort study

Author

Van't Klooster, Cilie C, Ridker, Paul M, Hjortnaes, Jesper, van der Graaf, Yolanda, Asselbergs, Folkert W, Westerink, Jan, Aerts, Joachim G J V, Visseren, Frank L J, and UCC-SMART Study Group

Subjects
Incident cancer, Patients with vascular disease, High-sensitive C-reactive protein, Journal Article, Chronic systemic low-grade inflammation, Risk factor, Cardiology and Cardiovascular Medicine
Abstract

AIMS: Low-grade inflammation, measured by elevated plasma concentrations of high-sensitive C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). There is evidence that low-grade inflammation is also related to a higher risk of cancer. The present prospective cohort study evaluates the relation between low-grade systemic inflammation and risk of cancer in patients with stable CVD. METHODS AND RESULTS: In total, 7178 patients with stable CVD and plasma CRP levels ≤10 mg/L were included. Data were linked to the Dutch national cancer registry. Cox regression models were fitted to study the relation between CRP and incident CVD and cancer. After a median follow-up time of 8.3 years (interquartile range 4.6-12.3) 1072 incident cancer diagnoses were observed. C-reactive protein concentration was related to total cancer [hazard ratio (HR) 1.35; 95% confidence interval (CI) 1.10-1.65] comparing last quintile to first quintile of CRP. Especially lung cancer, independent of histopathological subtype, was related to CRP (HR 3.39; 95% CI 2.02-5.69 comparing last to first quintile of CRP). Incidence of epithelial neoplasms and especially squamous cell neoplasms were related to CRP concentration, irrespective of anatomical location. Sensitivity analyses after excluding patients with a cancer diagnosis within 1, 2, and 5 years of follow-up showed similar results. No effect modification was observed by smoking status or time since smoking cessation (P-values for interaction > 0.05). CONCLUSION: Chronic systemic low-grade inflammation, measured by CRP levels ≤10 mg/L, is a risk factor for incident cancer, markedly lung cancer, in patients with stable CVD. The relation between inflammation and incident cancer is seen in former and current smokers and is uncertain in never smokers.

Published
2019

48. Integrative Multi-Omics Analysis in Calcific Aortic Valve Disease Reveals a Link to the Formation of Amyloid-Like Deposits

Author

Heuschkel, Marina A., primary, Skenteris, Nikolaos T., additional, Hutcheson, Joshua D., additional, van der Valk, Dewy D., additional, Bremer, Juliane, additional, Goody, Philip, additional, Hjortnaes, Jesper, additional, Jansen, Felix, additional, Bouten, Carlijn V.C., additional, van den Bogaerdt, Antoon, additional, Matic, Ljubica, additional, Marx, Nikolaus, additional, and Goettsch, Claudia, additional

Published
2020
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