Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfusion (IR) injury in the heart (and/or other organs) by brief episodes of non-lethal IR in a distant organ/tissue. Importantly, RIPC can be induced noninvasively by limitation of blood flow in the extremity implying the applicability of this method in clinical situations. RIPC (and its delayed phase) is a form of relatively short-term adaptation to ischemia, similar to ischemic PC, and likely they both share triggering mechanisms, whereas mediators and end-effectors may differ. It is hypothesized that communication between the signals triggered in the remote organs and protection in the target organ may be mediated through substances released from the preconditioned organ and transported via the circulation (humoral pathways), by neural pathways and/or via systemic anti-inflammatory and antiapoptotic response to short ischemic bouts. Identification of molecules involved in RIPC cascades may have therapeutic and diagnostic implications in the management of myocardial ischemia. Elucidation of the mechanisms of endogenous cardioprotection triggered in the remote organ could lead to the development of diverse pharmacological RIPC mimetics. In the present article, the authors provide a short overview of RIPC-induced protection, proposed underlying mechanisms and factors modulating RIPC as a promising cardioprotective strategy., T. Ravingerova, V. Farkasova, L. Griecsova, S. Carnicka, M. Murarikova, E. Barlaka, F. Kolar, M. Bartekova, L. Lonek, J. Slezak, A. Lazou., and Obsahuje bibliografii
Although physical exercise is known to reduce size of infarction,
incidence of ventricular arrhythmias, and to improve heart
function, molecular mechanisms of this protection are not fully
elucidated. We explored the hypothesis that voluntary running,
similar to adaptive interventions, such as ischemic or remote
preconditioning, may activate components of pro-survival (RISK)
pathway and potentially modify cell proliferation. Sprague-Dawley
adult male rats freely exercised for 23 days in cages equipped
with running wheels, while sedentary controls were housed in
standard cages. After 23 days, left ventricular (LV) myocardial
tissue samples were collected for the detection of expression and
activation of RISK proteins (WB). The day before, a marker of
cell proliferation 5-bromo-2'-deoxyuridine (BrdU) was given to all
animals to detect its incorporation into DNA of the LV cells
(ELISA). Running increased phosphorylation (activation) of Akt,
as well as the levels of PKCε and phospho-ERK1/2, whereas BrdU
incorporation into DNA was unchanged. In contrast, exercise
promoted pro-apoptotic signaling - enhanced Bax/Bcl-2 ratio and
activation of GSK-3β kinase. Results suggest that in the rat
myocardium adapted to physical load, natural cardioprotective
processes associated with physiological hypertrophy are
stimulated, while cell proliferation is not modified. Up-regulation
of pro-apoptotic markers indicates potential induction of cell
death mechanisms that might lead to maladaptation in the longterm.