Publications
Below you can find a list of our published research.
Below you can find a list of our published research.
44 results
Cited 3 times since 2020 (0.7 per year) source: EuropePMC
International journal of cardiology. Heart & vasculature, Volume 27, 17 3 2020, Pages 100499 Multifocal cardiovascular calcification in patients with established cardiovascular disease; prevalence, risk factors, and relation with recurrent cardiovascular disease. van 't Klooster CC, Nathoe HM, Hjortnaes J, Bots ML, Isgum I, Lessmann N, van der Graaf Y, Leiner T, Visseren FLJ, UCC-SMART-study group
Aims: The aim is to investigate (multifocal) cardiovascular calcification in patients with established cardiovascular disease (CVD), regarding prevalence, risk factors, and relation with recurrent CVD or vascular interventions. Coronary artery calcification (CAC), thoracic aortic calcification (TAC) (including ascending aorta, aortic arch, descending aorta), mitral annular calcification (MAC), and aortic valve calcification (AVC) are studied. Methods: The study concerned 568 patients with establ... Abstract
Cited 30 times since 2019 (6.7 per year) source: EuropePMC
European heart journal, Volume 40, Issue 48, 1 1 2019, Pages 3901-3909 The relation between systemic inflammation and incident cancer in patients with stable cardiovascular disease: a cohort study. Van't Klooster CC, Ridker PM, Hjortnaes J, van der Graaf Y, Asselbergs FW, Westerink J, Aerts JGJV, Visseren FLJ
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 we... Abstract
Cited 96 times since 2019 (19 per year) source: EuropePMC
Journal of the American College of Cardiology, Volume 73, Issue 17, 1 1 2019, Pages 2150-2162 Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis. Zheng KH, Tsimikas S, Pawade T, Kroon J, Jenkins WSA, Doris MK, White AC, Timmers NKLM, Hjortnaes J, Rogers MA, Aikawa E, Arsenault BJ, Witztum JL, Newby DE, Koschinsky ML, Fayad ZA, Stroes ESG, Boekholdt SM, Dweck MR
Background: Lipoprotein(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. Objectives: This 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 wi... Abstract
Cited 17 times since 2019 (3.4 per year) source: EuropePMC
Frontiers in cardiovascular medicine, Volume 6, 26 4 2019, Pages 52 Anti-fibrotic Effects of Cardiac Progenitor Cells in a 3D-Model of Human Cardiac Fibrosis. Bracco Gartner TCL, Deddens JC, Mol EA, Magin Ferrer M, van Laake LW, Bouten CVC, Khademhosseini A, Doevendans PA, Suyker WJL, Sluijter JPG, Hjortnaes J
Cardiac fibroblasts play a key role in chronic heart failure. The conversion from cardiac fibroblast to myofibroblast as a result of cardiac injury, will lead to excessive matrix deposition and a perpetuation of pro-fibrotic signaling. Cardiac cell therapy for chronic heart failure may be able to target fibroblast behavior in a paracrine fashion. However, no reliable human fibrotic tissue model exists to evaluate this potential effect of cardiac cell therapy. Using a gelatin methacryloyl hydroge... Abstract
Cited 2 times since 2018 (0.4 per year) source: EuropePMC
Injury, Volume 50, Issue 5, 6 1 2018, Pages 1036-1041 Identification of thoracic injuries by emergency medical services providers among trauma patients. van Rein EAJ, Lokerman RD, van der Sluijs R, Hjortnaes J, Lichtveld RA, Leenen LPH, van Heijl M
Introduction: Severe thoracic injuries are time sensitive and adequate triage to a facility with a high-level of trauma care is crucial. The emergency medical services (EMS) providers are required to identify patients with a severe thoracic injury to transport the patient to the right hospital. However, identifying these patients on-scene is difficult. The accuracy of prehospital assessment of potential thoracic injury by EMS providers of the ground ambulances is unknown. Therefore, the aim of t... Abstract
Cited 39 times since 2018 (6.5 per year) source: EuropePMC
Nanomaterials (Basel, Switzerland), Volume 8, Issue 5, 3 1 2018, Pages E296 Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics. van der Valk DC, van der Ven CFT, Blaser MC, Grolman JM, Wu PJ, Fenton OS, Lee LH, Tibbitt MW, Andresen JL, Wen JR, Ha AH, Buffolo F, van Mil A, Bouten CVC, Body SC, Mooney DJ, Sluijter JPG, Aikawa M, Hjortnaes J, Langer R, Aikawa E
In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and... Abstract
Cited 17 times since 2017 (2.5 per year) source: EuropePMC
Current treatment options in cardiovascular medicine, Volume 19, Issue 9, 1 1 2017, Pages 71 Current Challenges in Translating Tissue-Engineered Heart Valves. Stassen OMJA, Muylaert DEP, Bouten CVC, Hjortnaes J
Opinion statement: Heart valve disease is a major health burden, treated by either valve repair or valve replacement, depending on the affected valve. Nearly 300,000 valve replacements are performed worldwide per year. Valve replacement is lifesaving, but not without complications. The in situ tissue-engineered heart valve is a promising alternative to current treatments, but the translation of this novel technology to the clinic still faces several challenges. These challenges originate from th... Abstract
Cited 44 times since 2017 (6.3 per year) source: EuropePMC
Advanced healthcare materials, Volume 6, Issue 11, 12 2 2017 Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling. Sadeghi AH, Shin SR, Deddens JC, Fratta G, Mandla S, Yazdi IK, Prakash G, Antona S, Demarchi D, Buijsrogge MP, Sluijter JPG, Hjortnaes J, Khademhosseini A, Khademhosseini A
Activation of cardiac fibroblasts into myofibroblasts is considered to play an essential role in cardiac remodeling and fibrosis. A limiting factor in studying this process is the spontaneous activation of cardiac fibroblasts when cultured on two-dimensional (2D) culture plates. In this study, a simplified three-dimensional (3D) hydrogel platform of contractile cardiac tissue, stimulated by transforming growth factor-β1 (TGF-β1), is presented to recapitulate a fibrogenic microenvironment. It is... Abstract
Cited 16 times since 2016 (2.1 per year) source: EuropePMC
Advanced healthcare materials, Volume 6, Issue 3, 1 1 2016 Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models. Deddens JC, Sadeghi AH, Hjortnaes J, van Laake LW, Buijsrogge M, Doevendans PA, Khademhosseini A, Sluijter JP
Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the f... Abstract
Cited 11 times since 2016 (1.4 per year) source: EuropePMC
Seminars in thoracic and cardiovascular surgery, Volume 28, Issue 4, 5 1 2016, Pages 757-767 Comparative Histopathological Analysis of Mitral Valves in Barlow Disease and Fibroelastic Deficiency. Hjortnaes J, Keegan J, Bruneval P, Schwartz E, Schoen FJ, Carpentier A, Levine RA, Hagège A, Aikawa E
Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attac... Abstract
Cited 22 times since 2016 (2.8 per year) source: EuropePMC
ACS biomaterials science & engineering, Volume 3, Issue 9, 20 3 2016, Pages 1964-1971 Oxygen-Generating Photo-Cross-Linkable Hydrogels Support Cardiac Progenitor Cell Survival by Reducing Hypoxia-Induced Necrosis. Alemdar N, Leijten J, Camci-Unal G, Hjortnaes J, Ribas J, Paul A, Mostafalu P, Gaharwar AK, Qiu Y, Sonkusale S, Liao R, Khademhosseini A
Oxygen is essential to cell survival and tissue function. Not surprisingly, ischemia resulting from myocardial infarction induces cell death and tissue necrosis. Attempts to regenerate myocardial tissue with cell based therapies exacerbate the hypoxic stress by further increasing the metabolic burden. In consequence, implanted tissue engineered cardiac tissues suffer from hypoxia-induced cell death. Here, we report on the generation of oxygen-generating hydrogels composed of calcium peroxide (CP... Abstract
Cited 48 times since 2016 (5.9 per year) source: EuropePMC
Journal of molecular and cellular cardiology, Volume 94, 17 3 2016, Pages 13-20 Simulation of early calcific aortic valve disease in a 3D platform: A role for myofibroblast differentiation. Hjortnaes J, Goettsch C, Hutcheson JD, Camci-Unal G, Lax L, Scherer K, Body S, Schoen FJ, Kluin J, Khademhosseini A, Khademhosseini A, Aikawa E
Purpose: Calcific aortic valve disease (CAVD) is the most prevalent valve disease in the Western world. Recent difficulty in translating experimental results on statins to beneficial clinical effects warrants the need for understanding the role of valvular interstitial cells (VICs) in CAVD. In two-dimensional culture conditions, VICs undergo spontaneous activation similar to pathological differentiation, which intrinsically limits the use of in vitro models to study CAVD. Here, we hypothesized t... Abstract
Cited 54 times since 2016 (6.4 per year) source: EuropePMC
Journal of the American College of Cardiology, Volume 67, Issue 3, 1 1 2016, Pages 275-287 Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve. Dal-Bianco JP, Aikawa E, Bischoff J, Guerrero JL, Hjortnaes J, Beaudoin J, Szymanski C, Bartko PE, Seybolt MM, Handschumacher MD, Sullivan S, Garcia ML, Mauskapf A, Titus JS, Wylie-Sears J, Irvin WS, Chaput M, Messas E, Hagège AA, Carpentier A, Levine RA, Leducq Transatlantic Mitral Network
Background: In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition. Objectives: The aim of this study was to explore the clinically relevant situation of... Abstract
Cited 98 times since 2015 (11.1 per year) source: EuropePMC
Atherosclerosis, Volume 242, Issue 1, 17 3 2015, Pages 251-260 Valvular interstitial cells suppress calcification of valvular endothelial cells. Hjortnaes J, Shapero K, Goettsch C, Hutcheson JD, Keegan J, Kluin J, Mayer JE, Bischoff J, Aikawa E
Background: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. We previously proposed that valvular endothelial cells (VECs) replenish injured adult valve leaflets via endothelial-to-mesenchymal transformation (EndMT); however, whether EndMT contributes to valvular calcification is unknown. We hypothesized that aortic VECs undergo osteogenic differentiation via an EndMT process that can be inhibited by valvular interstitial cells (VICs). Approach an... Abstract
Cited 20 times since 2015 (2.1 per year) source: EuropePMC
Interactive cardiovascular and thoracic surgery, Volume 20, Issue 4, 22 4 2015, Pages 520-530 Mortality after cardiac surgery in patients with liver cirrhosis classified by the Child-Pugh score. Jacob KA, Hjortnaes J, Kranenburg G, de Heer F, Kluin J
Liver cirrhosis is a known risk factor for postoperative mortality in patients undergoing cardiac surgery. Clinical assessment of liver cirrhosis using the widely accepted Child-Pugh (CP) score is thus vital for evaluation of surgical options and perioperative care. However, detailed mortality rates as a consequence of liver cirrhosis are unclear. This review aimed to stratify the risk of short-term ( Abstract
Cited 43 times since 2014 (4.3 per year) source: EuropePMC
Advanced healthcare materials, Volume 4, Issue 1, 24 4 2014, Pages 121-130 Directing valvular interstitial cell myofibroblast-like differentiation in a hybrid hydrogel platform. Hjortnaes J, Camci-Unal G, Hutcheson JD, Jung SM, Schoen FJ, Kluin J, Aikawa E, Khademhosseini A
Three dimensional (3D) hydrogel platforms are powerful tools, providing controllable, physiologically relevant microenvironments that could aid in understanding how various environmental factors direct valvular interstitial cell (VIC) phenotype. Continuous activation of VICs and their transformation from quiescent fibroblast to activated myofibroblast phenotype is considered to be an initiating event in the onset of valve disease. However, the relative contribution VIC phenotypes is poorly under... Abstract
Cited 67 times since 2014 (6.8 per year) source: EuropePMC
Biomaterials, Volume 35, Issue 27, 16 3 2014, Pages 7774-7785 Tri-layered elastomeric scaffolds for engineering heart valve leaflets. Masoumi N, Annabi N, Assmann A, Larson BL, Hjortnaes J, Alemdar N, Kharaziha M, Manning KB, Mayer JE, Khademhosseini A
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 c... Abstract
Cited 325 times since 2014 (32.5 per year) source: EuropePMC
Lab on a chip, Volume 14, Issue 13, 23 4 2014, Pages 2202-2211 Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs. Bertassoni LE, Cecconi M, Manoharan V, Nikkhah M, Hjortnaes J, Cristino AL, Barabaschi G, Demarchi D, Dokmeci MR, Yang Y, Khademhosseini A
Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limite... Abstract
Cited 23 times since 2013 (2 per year) source: EuropePMC
Trends in cardiovascular medicine, Volume 23, Issue 3, 3 1 2013, Pages 71-79 Visualizing novel concepts of cardiovascular calcification. Hjortnaes J, New SE, Aikawa E
Cardiovascular calcification is currently viewed as an active disease process similar to embryonic bone formation. Cardiovascular calcification mainly affects the aortic valve and arteries and is associated with increased mortality risk. Aortic valve and arterial calcification share similar risk factors, including age, gender, diabetes, chronic renal disease, and smoking. However, the exact cellular and molecular mechanism of cardiovascular calcification is unknown. Late-stage cardiovascular cal... Abstract
The Journal of thoracic and cardiovascular surgery, Volume 144, Issue 2, 11 2 2012, Pages 506-508 Surgical treatment of residual systolic anterior motion after otherwise successful percutaneous transluminal septal myocardial ablation: a case report. Hjortnaes J, Leemans PA, ten Cate FJ, van Herwerden LA