No prominent role for complement C1-esterase inhibitor in Marfan syndrome mice.
Stijntje HibenderSiyu LiAlex V PostmaMyrthe E HoogelandDenise KlaverRichard B PouwHans W NiessenAntoine Hg DriessenDavid R KoolbergenCarlie Jm de VriesMarieke Jh BaarsArjan C HouwelingPaul A KrijnenVivian de WaardPublished in: Vascular biology (Bristol, England) (2022)
Marfan syndrome (MFS) is a connective tissue disorder causing aortic aneurysm formation. Currently, only prophylactic aortic surgery and blood pressure lowering drugs are available to reduce the risk for aortic rupture. Upon whole genome sequencing (WGS) of a Marfan family, we identified a complement gene C1R variant (p.Ser152Leu), which associated with the severe aortic patients. Therefore, we assessed the role of complement activation in MFS aortic tissue. Expression of various complement genes and proteins was detected in human and murine MFS aneurysm tissue, which prompted us to study complement inhibition in MFS mice. Treatment of the Fbn1C1041G/+ MFS mice with human plasma-derived C1-esterase inhibitor Cetor® resulted in reduced complement deposition, decreased macrophage influx in the aorta and lower circulating TNFα levels. However, in line with previous anti-inflammatory treatments, complement inhibition did not change aortic dilatation rate in this MFS mouse model. Thus, while complement factors/C3 activation were detected in human/murine MFS aorta, Cetor® had no effect on aortic dilatation in MFS mice, indicating that complement inhibition is not a suitable treatment strategy in MFS.
Keyphrases
- aortic valve
- aortic dissection
- pulmonary artery
- left ventricular
- blood pressure
- aortic aneurysm
- mouse model
- endothelial cells
- high fat diet induced
- end stage renal disease
- ejection fraction
- anti inflammatory
- pulmonary arterial hypertension
- heart failure
- newly diagnosed
- pulmonary hypertension
- poor prognosis
- gene expression
- induced pluripotent stem cells
- metabolic syndrome
- coronary artery disease
- early onset
- copy number
- transcription factor
- percutaneous coronary intervention
- peritoneal dialysis
- skeletal muscle
- patient reported
- drug induced
- long non coding rna
- surgical site infection