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This study characterizes in the right and left ventricle a differential regulation of the dominant PKC isozymes in pressure-overload cardiac hypertrophy both at the protein and the mRNA level.

An activation of protein kinase C (PKC) in acute myocardial ischemia has been shown previously using its translocation to the plasma membrane as an indirect parameter. However, whether PKC remains activated or whether other mechanisms such as altered gene expression may mediate an isozyme-specific regulation in prolonged ischemia have not been investigated. In isolated perfused rat hearts, PKC activity and the expression of PKC cardiac isozymes were determined on the protein level using enzyme activities and Western blot analyses and on the mRNA level using reverse transcriptase-polymerase chain reaction after various periods of global ischemia (1 to 60 minutes). As early as 1 minute after the onset of ischemia, PKC activity is translocated from the cytosol to the particulate fraction without change in total cardiac enzyme activity. This translocation involves all major cardiac isozymes of PKC (ie, PKCalpha, PKCdelta, PKCepsilon, and PKCzeta). This rapid, nonselective activation of PKCs is only transient. In contrast, prolonged ischemia (>/=15 minutes) leads to an increased cardiac PKC activity (119+/-7 versus 190+/-8 pmol/min per mg protein) residing in the cytosol. This is associated with an augmented, subtype-selective isozyme expression of PKCdelta and PKCvarepsilon (163% and 199%, respectively). The specific mRNAs for PKCdelta (948+/-83 versus 1501+/-138 ag/ng total RNA, 30 minutes of ischemia) and PKCepsilon (1597+/-166 versus 2611+/-252 ag/ng total RNA) are selectively increased. PKCalpha and PKCzeta remain unaltered. In conclusion, two distinct activation and regulation processes of PKC are characterized in acute myocardial ischemia. The early, but transient, translocation involves all constitutively expressed cardiac isozymes of PKC, whereas in prolonged ischemia an increased total PKC activity is associated with an isozyme-selective induction of PKCepsilon and PKCdelta. Whether these fundamentally different activation processes interact remains to be elucidated.

AimsIn the IN-TIME trial, automatic daily implant-based multiparameter telemonitoring significantly improved clinical outcomes in patients with chronic systolic heart failure and implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D). We compared IN-TIME results for ICD and CRT-D subgroups.MethodsPatients with LVEF ≤ 35%, NYHA class II/III, optimized drug treatment, no permanent atrial fibrillation, and a dual-chamber ICD (n = 274) or CRT-D (n = 390) were randomized 1:1 to telemonitoring or no telemonitoring for 12 months. Primary outcome measure was a composite clinical score, classified as worsened if the patient died or had heart failure-related hospitalization, worse NYHA class, or a worse self-reported overall condition.ResultsThe prevalence of worsened score at study end was higher in CRT-D than ICD patients (26.4% vs. 18.2%; P = 0.014), as was mortality (7.4% vs. 4.1%; P = 0.069). With telemonitoring, odds ratios (OR) for worsened score and hazard ratios (HR) for mortality were similar in the ICD [OR = 0.55 (P = 0.058), HR = 0.39 (P = 0.17)] and CRT-D [OR = 0.68 (P = 0.10), HR = 0.35 (P = 0.018)] subgroups (insignificant interaction, P = 0.58–0.91).ConclusionDaily multiparameter telemonitoring has a potential to reduce clinical endpoints in patients with chronic systolic heart failure both in ICD and CRT-D subgroups. The absolute benefit seems to be higher in higher-risk populations with worse prognosis.Electronic supplementary materialThe online version of this article (10.1007/s00392-019-01447-5) contains supplementary material, which is available to authorized users.

Inhibition of angiotensin-converting enzyme (ACEI) after myocardial infarction reduces remodeling of the surviving myocardium. The cellular signaling mechanisms contributing to remodeling are not fully elucidated. Goal of the current study was to test whether protein kinase C (PKC) is regulated in the surviving myocardium shortly after infarction and whether this regulation is influenced by ACEI. Rats were subjected to anterior wall myocardial infarction in vivo or sham operation. After 15-45 min, mRNA levels and protein expression of the major cardiac PKC isoforms were measured in the ischemic and the remote myocardium. The influence of ACEI on PKC was tested by pretreating the rats with ramiprilat. In the ischemic region of the myocardium, a significant increase of the mRNA for PKC-delta and PKC-epsilon was observed in close correlation with increased isoform protein expression. In the surviving, remote myocardium, however, only PKC-epsilon expression was significantly augmented both at the mRNA level (158%) and at the protein level (149%). PKC-delta and PKC-alpha were unchanged. Treatment with ramiprilat could abolish this isoform-specific PKC regulation in both areas. These data characterize for the first time an isoform-specific transcriptional regulation process of PKC in the surviving myocardium after infarction. This induction of PKC-epsilon can be prevented by ACEI. It is speculated that PKC-epsilon plays a role in the signal transduction of early remodeling after infarction.