Abstract
In vascular smooth muscle cells (VSMCs) integrin-mediated adhesion to extracellular matrix (ECM) proteins play important roles in sustaining vascular tone and resistance. The main goal of this study was to determine whether VSMCs adhesion to type I collagen (COL-I) was altered in parallel with the changes in the VSMCs contractile state induced by vasoconstrictors and vasodilators. VSMCs were isolated from rat cremaster skeletal muscle arterioles and maintained in primary culture without passage. Cell adhesion and cell E-modulus were assessed using atomic force microscopy (AFM) by repetitive nano-indentation of the AFM probe on the cell surface at 0.1 Hz sampling frequency and 3200 nm Z-piezo travelling distance (approach and retraction). AFM probes were tipped with a 5 μm diameter microbead functionalized with COL-I (1mg\\ml). Results showed that the vasoconstrictor angiotensin II (ANG-II; 10−6) significantly increased (p<0.05) VSMC E-modulus and adhesion probability to COL-I by approximately 35% and 33%, respectively. In contrast, the vasodilator adenosine (ADO; 10−4) significantly decreased (p<0.05) VSMC E-modulus and adhesion probability by approximately −33% and −17%, respectively. Similarly, the NO donor (PANOate, 10−6 M), a potent vasodilator, also significantly decreased (p<0.05) the VSMC E-modulus and COL-I adhesion probability by −38% and −35%, respectively. These observations support the hypothesis that integrin-mediated VSMC adhesion to the ECM protein COL-I is dynamically regulated in parallel with VSMC contractile activation. These data suggest that the signal transduction pathways modulating VSMC contractile activation and relaxation, in addition to ECM adhesion, interact during regulation of contractile state.
Highlights
The contractile state of vascular smooth muscle cells (VSMC) determines resistance vessel diameter, which is critical to regulation of tissue blood flow and blood pressure
As the generation of force by VSMC involves transmission of mechanical force between the cell and the extracellular environment, we hypothesized that changes in the contractile state of VSMC would be accompanied by parallel changes in adhesion to the extracellular matrix (ECM)
Integrin-mediated cell adhesion to ECM at focal adhesion sites has been identified as one major mechanosensory site as well as an important region for transmission of mechanical forces and cell signals [20,23]
Summary
The contractile state of vascular smooth muscle cells (VSMC) determines resistance vessel diameter, which is critical to regulation of tissue blood flow and blood pressure. Adhesion to the ECM is largely regulated by integrins that are a large family of heterodimeric cell adhesion molecules that anchor cells to ECM and neighboring cells They play key roles in many biological processes including cell motility, cytoskeleton organization, mediating the cell-cell and cell-ECM signals transduction [1,2,3,4,5,6,7,8]. Collagen (COL) is one of the major structural components of ECM within vascular wall and binds to a number of different integrins [9,10,11,12]. Integrin activation through inside-out signaling is a well-accepted mechanism for modulation of integrin activation and adhesion with the ECM [15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
