Molecular and cellular characterization of cardiac overload-induced hypertrophy and failure

Umar, S. (2009)

Doctoral Thesis

In neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects of phenylephrine (chapter 2). Ventricular failure is associated with disturbed collagen turnover. Myocardial collagen turnover can be assessed by plasma PINP, PIIINP, and ICTP representing collagen synthesis (PINP, PIIINP) or degradation (ICTP). We investigated the effects of cardiac resynchronization therapy (CRT) on collagen turnover in patients at baseline and after 6 months of CRT (chapter 3). Monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and RV failure are associated with MMP activation in RV, we investigated whether NO plays role in RV hypertrophy and failure (chapter 4). In chapter 5 we reviewed novel approaches to treat experimental PAH. We investigated whether MCT-induced PAH and RV failure can be treated with mesenchymal stem cells (MSCs) from donor rats with PAH caused by MCT. At day 14 after MCT, recipient rats were treated with MSCs. In chapters 6,7 the effects of MSCs on pulmonary pathology and RV function were examined. Isolated cardiomyocytes were investigated for PAH-related changes in excitability. In chapter 8 we reported on excitability properties dependent on Kv-channel expression, proposed to play a role in arrhythmias.

• Integrins
• Stem cells
• Pulmonary hypertension
• Hypertrophy
• Heart failure
• Resynchronization therapy
• Collagen
• MMP
• Signaling

• All authors: Umar, S.
• Supervisor: Laarse, A. van der
• Co-supervisor: Atsma, D.E.; Steendijk, P.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2009-06-18
• ISBN (print): 9789090242989