A negative relationship exists between diabetes mellitus (DM) and abdominal aortic
aneurysms (AAA), which is possibly caused by use of metformin. The aim of this study is to
examine the difference in smooth muscle cell (SMC) contractile phenotype, proliferation
capacity and metabolic activity of non-pathologic aortic controls, non-diabetic AAA patients
and diabetic AAA patients. In addition, we investigate the therapeutic effect of metformin on
these SMC functions.
Aortic biopsies were perioperative obtained from AAA patients (n = 20) and controls (n = 15).
SMCs of non-pathologic aortic controls, non-diabetic AAA patients and diabetic AAA patients
were treated with 10 mM metformin and a selection left untreated as negative control. After
five days metabolic activity measurement was done with the WST-1 assay and proliferation
was evaluated by counting the amount of produced protein. The contractility was tested using
Electric Cell-substrate Impedance Sensing (ECIS) upon ionomycin stimulation after 60 hours of
metformin treatment.
No significant difference was seen in baseline contractility, proliferation and metabolic activity
in SMCs of the three study groups. However, metformin had a significant effect on the tested
SMC functions. Metformin elevated the contraction in SMC of controls (n=11), non-diabetic
AAA patients (n=11) and diabetic AAA patients (n=4) (p<0.068). The contraction increased
significant (p=0.004) after treatment with metformin in SMCs of non-diabetic AAA patients [Figure 1].
Furthermore, a significant increase of metabolic activity (p<0.028) and a significant decrease
of proliferation capacity (p<0.018) was found in SMCs of controls (n=15), non-diabetic AAA
patients (n=13) and diabetic AAA patients (n=7) after treatment with metformin.
Metformin treatment has a direct effect on SMC function of AAA patients by decreasing
proliferation capacity and increasing contractility and metabolic activity. We will expand the
sample size and complement the research groups. Activation of AMPK signaling pathway is
proposed to be responsible for multiple positive effects of metformin. We will perform a small
interfering RNA knockdown of the AMPKα pathway to explicate possible other involved
pathways and we hope to identify more therapeutic targets of Metformin in AAA with whole
genome sequencing.