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Principal Investigators
Career Opportunities
Prof. Dr. Daphne Merkus

Our research focuses on the role of microvascular dysfunction in the development and progression of cardiovascular disease. Microvascular dysfunction not only impacts organ perfusion, but also results in paracrine effects contributing to organ dysfunction. Moreover, the microcirculation is an important entry-point for circulating neuro-humoral as well as inflammatory factors/ toxins into different organs.
It is increasingly recognized that chronic kidney disease impairs microvascular function in the heart, causes low-grade inflammation, oxidative stress and interstitial fibrosis and thereby predisposes to development of heart failure. The effect of chronic kidney disease on cardiac (dys)function is studied in our group using swine models of diabetes and chronic kidney disease.
In addition, we are interested in changes in the pulmonary vasculature and the heart in response to pulmonary hypertension. Using various swine models of pulmonary hypertension, we have recently shown that impaired myocardial perfusion and molecular changes in the right ventricle correlate with the inability of the right ventricle to cope with its increased work load during exercise.

Members of the Merkus Team: 


Recent publications:

Intervening with the Nitric Oxide Pathway to Alleviate Pulmonary Hypertension in Pulmonary Vein Stenosis.
van Duin RWB, Stam K, Uitterdijk A, Bartelds B, Danser AHJ, Reiss IKM, Duncker DJ, Merkus D.
J Clin Med. 2019 Aug 12;8(8). pii: E1204. doi: 10.3390/jcm8081204.

Right Ventricular Oxygen Delivery as a Determinant of Right Ventricular Functional Reserve during Exercise in Juvenile Swine with Chronic Pulmonary Hypertension.
Cai Z, van Duin RWB, Stam K, Uitterdijk A, van der Velden J, Vonk-Noordegraaf A, Duncker DJ, Merkus D.
Am J Physiol Heart Circ Physiol. 2019 Aug 9. doi: 10.1152/ajpheart.00130.2019. [Epub ahead of print]

Placental effects and transfer of sildenafil in healthy and preeclamptic conditions.
Hitzerd E, Broekhuizen M, Mirabito Colafella KM, Glisic M, de Vries R, Koch BCP, de Raaf MA, Merkus D, Schoenmakers S, Reiss IKM, Danser AHJ, Simons SHP.
EBioMedicine. 2019 Jul;45:447-455. doi: 10.1016/j.ebiom.2019.06.007. Epub 2019 Jun 14.

Cardiac remodelling in a swine model of chronic thromboembolic pulmonary hypertension: comparison of right vs. left ventricle.
Stam K, Cai Z, van der Velde N, van Duin R, Lam E, van der Velden J, Hirsch A, Duncker DJ, Merkus D.
J Physiol. 2019 Sep;597(17):4465-4480. doi: 10.1113/JP277896. Epub 2019 Jul 25.

Validation of 4D flow CMR against simultaneous invasive hemodynamic measurements: a swine study.
Stam K, Chelu RG, van der Velde N, van Duin R, Wielopolski P, Nieman K, Merkus D, Hirsch A.
Int J Cardiovasc Imaging. 2019 Jun;35(6):1111-1118. doi: 10.1007/s10554-019-01593-x. Epub 2019 Apr 8.

Human Placental Vascular Reactivity in Health and Disease: Implications for the Treatment of Pre-eclampsia.
Hitzerd E, Broekhuizen M, Neuman RI, Colafella KMM, Merkus D, Schoenmakers S, Simons SHP, Reiss IKM, Danser AHJ.
Curr Pharm Des. 2019;25(5):505-527. doi: 10.2174/1381612825666190405145228.

Protease-activated receptor 1 as potential therapeutic target in pulmonary arterial hypertension.
Merkus D, van Beusekom HMM, Boomars KA.
Cardiovasc Res. 2019 Jul 1;115(8):1260-1261. doi: 10.1093/cvr/cvz071. No abstract available. 

Differential impact of severe familial hypercholesterolemia on regional skeletal muscle and organ blood flows during exercise: Effects of PDE5 inhibition.
Aragonez CG, de Beer VJ, Tharp DL, Bowles DK, Laughlin MH, Merkus D, Duncker DJ, Bender SB.
Microcirculation. 2019 Aug;26(6):e12539. doi: 10.1111/micc.12539. Epub 2019 Mar 26.

Uridine adenosine tetraphosphate and purinergic signaling in cardiovascular system: An update.
Zhou Z, Matsumoto T, Jankowski V, Pernow J, Mustafa SJ, Duncker DJ, Merkus D.
Pharmacol Res. 2019 Mar;141:32-45. doi: 10.1016/j.phrs.2018.12.009. Epub 2018 Dec 13. Review.

Changes in the nitric oxide pathway of the pulmonary vasculature after exposure to hypoxia in swine model of neonatal pulmonary vascular disease.
de Wijs-Meijler DPM, Duncker DJ, Danser AHJ, Reiss IKM, Merkus D.
Physiol Rep. 2018 Oct;6(20):e13889. doi: 10.14814/phy2.13889.

Pulmonary microvascular remodeling in chronic thrombo-embolic pulmonary hypertension.
Stam K, van Duin RW, Uitterdijk A, Krabbendam-Peters I, Sorop O, Danser AHJ, Duncker DJ, Merkus D.
Am J Physiol Lung Cell Mol Physiol. 2018 Dec 1;315(6):L951-L964. doi: 10.1152/ajplung.00043.2018. Epub 2018 Sep 27.

Transition from post-capillary pulmonary hypertension to combined pre- and post-capillary pulmonary hypertension in swine: a key role for endothelin.
van Duin RWB, Stam K, Cai Z, Uitterdijk A, Garcia-Alvarez A, Ibanez B, Danser AHJ, Reiss IKM, Duncker DJ, Merkus D.
J Physiol. 2019 Feb;597(4):1157-1173. doi: 10.1113/JP275987. Epub 2018 Jun 21.

Uridine Adenosine Tetraphosphate-Induced Coronary Relaxation Is Blunted in Swine With Pressure Overload: A Role for Vasoconstrictor Prostanoids.
Zhou Z, Lankhuizen IM, van Beusekom HM, Cheng C, Duncker DJ, Merkus D.
Front Pharmacol. 2018 Mar 26;9:255. doi: 10.3389/fphar.2018.00255. eCollection 2018.

Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening.
Sorop O, Heinonen I, van Kranenburg M, van de Wouw J, de Beer VJ, Nguyen ITN, Octavia Y, van Duin RWB, Stam K, van Geuns RJ, Wielopolski PA, Krestin GP, van den Meiracker AH, Verjans R, van Bilsen M, Danser AHJ, Paulus WJ, Cheng C, Linke WA, Joles JA, Verhaar MC, van der Velden J, Merkus D, Duncker DJ.
Cardiovasc Res. 2018 Jun 1;114(7):954-964. doi: 10.1093/cvr/cvy038.