Costameres, dense plaques and podosomes: the cell matrix adhesions in cardiovascular mechanosensing

Abstract

The stiffness of the cardiovascular environment changes during ageing and in disease and contributes to disease incidence and progression. For instance, increased arterial stiffness can lead to atherosclerosis, while stiffening of the heart due to fibrosis can increase the chances of heart failure. Cells can sense the stiffness of the extracellular matrix through integrin adhesions and other mechanosensitive structures and in response to this initiate mechanosignalling pathways that ultimately change the cellular behaviour. Over the past decades, interest in mechanobiology has steadily increased and with this also our understanding of the molecular basis of mechanosensing and transduction. However, much of our knowledge about the mechanisms is derived from studies investigating focal adhesions in non-muscle cells, which are distinct in several regards from the cell-matrix adhesions in cardiomyocytes (costameres) or vascular smooth muscle cells (dense plaques or podosomes). Therefore, we will look here first at the evidence for mechanical sensing in the cardiovascular system, before comparing the different cytoskeletal arrangements and adhesion sites in cardiomyocytes and vascular smooth muscle cells and what is known about mechanical sensing through the various structures.

Keywords: Cardiomyocytes; Costameres; Dense plaques; Mechanosensing; Podosomes; Smooth muscle cells.

Fig. 1

The cardiomyocyte costamere. The sarcomeres are connected to the ECM through integrins, the dystrophin-glycoprotein complex (DGC) and desmin. a Side view of cardiomyocyte with thin filaments in red and thick filaments in light blue as well as Z-discs in grey and costamer in purple. b Side view of a costamere with the adhesion complex (i.e. talin, vinculin and other adaptor as well as signalling molecules) in purple, the DGC in orange and the desmin intermediate filaments in lime green. Arrows indicate the contractile forces from myofibrillar and non-myofibrillar structures. nmM non-muscle myosin. (Color figure online)

Fig. 2

Vascular smooth muscle cell adhesions. a Top view of a VSCM, with dense bodies in grey, dense plaques in purple and podosomes in green. b Side view of dense plaques attached to contractile stress fibres and dense bodies in the cytoplasm. Arrows indicate contractile forces of the stress fibres. c Side view of a podosome. The forces of the protrusive core with branched actin, as well as the tensile force from the adhesion ring are indicated by arrows. (Color figure online)