Atheroprotective IgM-Secreting B1a Lymphocytes (p 830)
Boosting B1a cells could be one way to subdue atherosclerosis, say Kyaw et al.
Although B lymphocytes collectively are known to put up a fight against atherosclerosis, the B2 lymphocytes, when transferred into atherosclerosis-prone mice, worsen the condition. Kyaw et al thus wondered which type of B cells were the do-gooders. Their prime suspect was B1a cells because depletion of these cells after splenectomy increases the risk for heart disease and atherosclerosis. Sure enough, transfer of B1a cells into splenectomized mice suffering from atherosclerosis improved their symptoms. In particular, the necrotic cores of atherosclerotic lesions were reduced in size and contained fewer dead cells. B1a cells are major producers of IgM antibodies and the team found that the level of IgM in plasma and in atherosclerotic lesions was reduced after splenectomy and restored after B1a transfer. Furthermore, transfer of B1a cells that could not secrete IgM did not improve atherosclerosis symptoms in the splenectomized mice. Kyaw et al conclude that expanding the number of B1a cells while diminishing B2 lymphocytes may be an effective therapeutic strategy against atherosclerosis.
Myocytes From LQTS 3–Specific iPS Cells (p 841)
Malan et al have made induced pluripotent stem (IPS) cells from a mouse model of human arrhythmia.
Long QT syndrome (LQTS) is a disorder of the heart whereby cardiomyocytes are slow to repolarize and have prolonged action potentials, which can cause serious and sometimes fatal arrhythmias. A number of ion channel mutations have been identified to cause LQTS, but obtaining heart cells from patients to study the disease is not easy. Deriving iPS cells from patients' fibroblast cells and differentiating them to become cardiomyocytes offers an alternative source of cells for study. Such derivations have been achieved from patients with LQTS 1 and 2 mutations. Now Malan et al have derived iPS cells from mice carrying the human LQTS 3 mutation. In this proof-of-principle paper, the authors showed that LQTS 3 iPS cells could be differentiated into cardiomyocytes that displayed the hallmark electrophysiology of the disease. The next step will be to derive iPS cells from LQTS 3 patients. In the meantime, the mouse iPS cells provide a convenient resource for studying disease mechanisms and screening drugs, as well as reducing the need for animal experiments.
miR-133 and Vascular Smooth Muscle Cells (p 880)
Torella et al have discovered a microRNA that can stop detrimental vessel cell division.
MicroRNAs (miRs) are small non-coding RNA molecules that bind to and suppress expression of specific target mRNAs. As such, miRs are responsible for controlling an array of cellular processes. Torella et al were studying the process of phenotype switching—the switch from quiescence to proliferation and migration—in vascular smooth muscle cells (VSMCs) and wondered which miRs might be involved. They studied a pair of miRs, miR-1 and miR-133, which are expressed from the same gene (bicistronic) and are important in cardiac and skeletal muscle cells. Their function in VSMCs was hitherto unknown. The team showed that only miR-133 was expressed in VSMCs, whereas miR-1 expression was negligible. Expression of miR-133 dropped when VSMCs started to proliferate, and overexpression of miR-133 could prevent both proliferation and migration. MiR-133 targeted the mRNAs of the transcription factor Sp-1 and the actin-binding protein moesin, which promote proliferation and migration, respectively. VSMC proliferation is necessary for blood vessel repair but can be pathological if overgrowth occurs, such as in atherosclerosis and restenosis. The authors suggest that activating miR-133 in these instances could be clinically advantageous.
Written by Ruth Williams.
- © 2011 American Heart Association, Inc.