Growth of Engineered Human Myocardium (p 47)
Stress and vessel cells are key ingredients when engineering human heart tissue, say Tulloch et al.
Studies in model organisms show that mechanical stress is essential for correct cardiac development, as of course is vascularization. But Tulloch et al wanted to know how these factors affected human myocardial development. They grew human ES- and iPS-derived cardiomyocytes on 3D collagen matrices that were either fixed at both ends—providing a resistant structure for the cells to pull against when contracting—or loose at one end, providing no resistance. With resistance, the cardiomyocytes aligned themselves in the direction of the applied force, increased in size (hypertrophy) and increased their proliferation rate. Without resistance, they did not. Furthermore, adding vascular cells to the culture also increased cardiomyocyte proliferation. This occurred irrespective of the stress applied. Interestingly, the vascular cells self-organized into vessel-like structures in the collagen/cardiomyocyte tissue. When this tissue was engrafted onto rat hearts, the vessel structures appeared to transport blood after just one week. Such 3D matrix culturing of human ES- and IPS-derived cardiomyocytes not only offers insight into cardiac development, but may also be useful for developing therapeutic repair strategies, say the authors.
Model of Canine Purkinje Cell Cycling (p 71)
Li and Rudy have built a mathematical model of a Purkinje cell to help understand the role of these cells in arrhythmogenic vulnerability.
Purkinje fibers of the heart are specialized muscle fibers essential for rapidly conducting electrical impulses from the sinoatrial node (pacemaker) across the myocardium to coordinate chamber contractions. However, Purkinje fiber cells are also implicated in a number of cardiac arrhythmias. This is thought to be because Purkinje fiber cells are intrinsically more vulnerable to arrhythmic activity than regular cardiomyocytes. To understand this vulnerability, Li and Rudy incorporated data on canine Pukinje cell electrophysiology and intracellular calcium fluctuations into a mathematical Purkinje cell model. Importantly, they also included information on the type and subcellular distribution of ryanodine receptors—protein channels that control calcium release from intracellular stores. Such information had been omitted from previous Purkinje cell models but affected the timing and type of calcium fluctuations, and thus, action potentials, observed in the team's new simulations. The new model should prove useful for developing an in-depth understanding of Purkinje cell electrical behavior and possibly for designing novel antiarrhythmic approaches.
Pannexin1 in the Regulation of Vasoconstriction (p 80)
Vessel cells coordinate contraction with the help of pannexin 1 protein, report Billaud et al.
Vascular smooth muscle cells (VSMCs) must coordinate their contractile behavior to increase or decrease peripheral resistance to blood flow. A particular type of physical connection between cells—called a gap junction—is thought to be involved, but Billaud et al were not convinced that this was the entire story. They observed that VSMCs in a small mouse artery were not as tightly packed as those in the aorta. And, sure enough, the team could not detect gap junctions in these smaller arteries, while gap junctions were abundant in the aorta. The team did find pannexin 1, however. Pannexin proteins are membrane channels that are known to regulate cell-to-cell communications by release of purines and, thus, do not require cells to be in such close quarters. The team found that pannexin 1 regulated VSMC contraction mediated by α1-adrenergic receptors but not mediated by KCl stimulation. They also showed that pannexin 1 and the α1-adrenergic receptor physically interacted and colocalized at the VSMC membrane. This discovery of a novel communication mechanism controlling small artery VSMC contraction could have implications for the development of antihypertensive therapies.
Written by Ruth Williams
- © 2011 American Heart Association, Inc.