Real-time monitoring of the effects of telmisartan on angiotensin II-induced mechanical changes in live mesangial cells using atomic force microscopy.
OBJECTIVE
Recent studies have shown that angiotensin II (Ang II) type 1 receptor blockers (ARB) may provide renal protection independent of their blood pressure-lowering effect. However, evidence for this comes from indirect methods, such as genetic or protein expression studies. In this study, we hypothesized that telmisartan, a specific ARB, applied to Ang II-stimulated mesangial cell (MC) would exert a renoprotective effect via modulation of MCs' mechanical properties.


METHODS
We investigated the effect of telmisartan on Ang II-induced changes in MCs utilizing real-time atomic force microscopy (AFM) imaging and force-distance curve measurements.


RESULTS
Real-time AFM images of live MCs demonstrated that cells contracted towards the center after Ang II exposure, and telmisartan treatment abolished this change. Cellular spring constants showed that telmisartan prevented Ang II-induced MC stiffening (Ang II: 0.109 ± 0.019 N/m, Ang II + telmisartan: 0.051 ± 0.016 N/m, p < 0.005). Telmisartan-treated MCs had a significantly lower adhesion force than those of the control group (control: 0.49 ± 0.22 nN, telmisartan: 0.22 ± 0.06 nN, Ang II: 0.40 ± 0.25 nN, Ang II + telmisartan: 0.27 ± 0.14 nN, p < 0.005). These results demonstrate that the dynamic contraction and mechanical properties of Ang II-stimulated MCs are restored by telmisartan.


CONCLUSIONS
We report for the first time the use of AFM force-distance curves on live MCs to directly monitor changes in surface adhesion and stiffness of cells after treatment with telmisartan in real time.
Department of Nephrology, College of Medicine, Kyung Hee University, Seoul, Korea.
Kyung-Hwan
KH
Jeong
Tae-Won
TW
Lee
Chun-Gyoo
CG
Ihm
Joo-Young
JY
Moon
Gi-Ja
GJ
Lee
Hun-Kuk
HK
Park
Sang-Ho
SH
Lee
D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D003199:Computer Systems; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D018625:Microscopy, Atomic Force / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan; D016896:Treatment Outcome
D001562:Benzimidazoles; D001565:Benzoates; D000804:Angiotensin II; D000077333:Telmisartan