Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple signaling pathways involving protein kinase C (PKC) have been implicated in the development of cardiac hypertrophy. We observed that a putative PKC inhibitor, PICOT (PKC-Interacting Cousin Of Thioredoxin) was upregulated in response to hypertrophic stimuli both in vitro and in vivo. This suggested that PICOT may act as an endogenous negative feedback regulator of cardiac hypertrophy through its ability to inhibit PKC activity, which is elevated during cardiac hypertrophy. Adenovirus-mediated gene transfer of PICOT completely blocked the hypertrophic response of neonatal rat cardiomyocytes to enthothelin-1 and phenylephrine, as demonstrated by cell size, sarcomere rearrangement, atrial natriuretic factor expression, and rates of protein synthesis. Transgenic mice with cardiac-specific overexpression of PICOT showed that PICOT is a potent inhibitor of cardiac hypertrophy induced by pressure overload. In addition, PICOT overexpression dramatically increased the ventricular function and cardiomyocyte contractility as measured by ejection fraction and end-systolic pressure of transgenic hearts and peak shortening of isolated cardiomyocytes, respectively. Intracellular Ca(2+) handing analysis revealed that increases in myofilament Ca(2+) responsiveness, together with increased rate of sarcoplasmic reticulum Ca(2+) reuptake, are associated with the enhanced contractility in PICOT-overexpressing cardiomyocytes. The inhibition of cardiac remodeling by of PICOT with a concomitant increase in ventricular function and cardiomyocyte contractility suggests that PICOT may provide an efficient modality for treatment of cardiac hypertrophy and heart failure.
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PMID:PICOT inhibits cardiac hypertrophy and enhances ventricular function and cardiomyocyte contractility. 1688 46

Cardiac hypertrophy is considered an early hallmark during the clinical course of heart failure and an important risk factor for cardiac morbidity and mortality. Although hypertrophy of individual cardiomyocytes in response to pathological stimuli has traditionally been considered as an adaptive response required to sustain cardiac output, accumulating evidence from studies in patients and animal models suggests that in most instances hypertrophy of the heart also harbors maladaptive aspects. Major strides have been made in our understanding of the pathways that convey pro-hypertrophic signals from the outside of the cell to the nucleus. In recent years it also has become increasingly evident that the heart possesses a variety of endogenous feedback mechanisms to counterbalance this growth response. These repressive mechanisms are of particular interest since they may provide valuable therapeutic options. In this review we summarize currently known endogenous repressors of pathological cardiac growth as they have been studied by gene targeting in mice. Many of the repressors that function in signal transduction appear to regulate calcineurin (e.g. PICOT, calsarcin, RCAN) and JNK signaling (e.g. CDC42, MKP-1) and some will be described in greater detail in this review. In addition, we will focus on factors such as Kruppel-like factors (KLF4, KLF15 and KLF10) and histone deacetylases (HDACs), which constitute a relevant group of nuclear proteins that repress transcription of the hypertrophic gene program in cardiomyocytes.
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PMID:Tapping the brake on cardiac growth-endogenous repressors of hypertrophic signaling. 2158 93

We conducted a meta-analysis of twenty-six randomized controlled trials that tested the effectiveness of home telemonitoring in patients with heart failure for reducing mortality and hospital use. We used the PICOT framework as a tool to address an important variable not previously studied: the timing or duration of monitoring. Specifically, we found that home telemonitoring decreased the odds of all-cause mortality and heart failure-related mortality at 180 days but not at 365 days. Home telemonitoring did not significantly affect the odds of all-cause hospitalization at 90 or 180 days, or of heart failure-related hospitalization at 180 days. At 180 days, home telemonitoring significantly increased the odds of all-cause emergency department visits. Home care provision did not moderate the effects of home telemonitoring on all-cause hospitalization. Recent regulatory changes that relaxed Medicare restrictions on telehealth reimbursement make it imperative that studies fully describe outcomes (for example, heart failure-related versus all-cause hospitalizations) and deliberately test all essential intervention elements, such as intervention duration.
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PMID:Home Telemonitoring In Heart Failure: A Systematic Review And Meta-Analysis. 3063 80