Abstract:The myocardial response to exercise is an adaptive mechanism that permits the heart to maintain cardiac output via improved cardiac function and development of hypertrophy. There are many overlapping mechanisms via which this occurs with calcium handling being a crucial component of this process. Our laboratory has previously found that the stretch sensitive TRPV2 channels are active regulators of calcium handling and cardiac function under baseline conditions based on our observations that TRPV2-KO mice have … Show more
“…Our data support previous reports regarding the mildly-attenuated cardiac performance in TRPV2-KO mice compared to their WT counterparts [ 15 , 16 ]. Moreover, Katanosaka and his colleagues have recently reported that heart-specific elimination of TRPV2 may be critically detrimental to cardiac structure and function in mice [ 29 ].…”
Section: Discussionsupporting
confidence: 93%
“…First, we wished to analyze whether TRPV2-WT and TRPV2-KO animals demonstrate any differences in cardiac function as previously suggested [ 15 , 16 ]. To this end, TRPV2-WT and KO male mice aged 12–16 weeks (6/arm) were studied by echocardiography.…”
BackgroundWe have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3–5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel.PurposeAssess cardiac function in TRPV2-KO mice compared to TRPV2-WT following AMI and analyze the potential involvement of TRPV2-expressing macrophages in the recovery process.MethodsTRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). In another set of experiments, TRPV2-KO mice induced with AMI, were intravenously (IV) injected with WT or TRPV2-KO peritoneal macrophages in order to directly assess the potential contribution of TRPV2-expressing macrophages to cardiac healing. Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative changes in the ejection fraction (EF) and additional cardiac parameters between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS).ResultsThe in vivo study showed that while EF was significantly decreased in the WT animals between baseline and day 30, EF was only slightly and insignificantly reduced in the KO animals. Likewise LVESD and LVESA were significantly modified exclusively in the WT animals. Moreover, intravenous administration of peritoneal WT macrophages, but not KO macrophages, significantly reduced survival of post-MI TRPV2-KO mice.ConclusionThe data suggest that knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery. TRPV2 may thus represent a novel therapeutic target for treatment of patients undergoing an acute MI.
“…Our data support previous reports regarding the mildly-attenuated cardiac performance in TRPV2-KO mice compared to their WT counterparts [ 15 , 16 ]. Moreover, Katanosaka and his colleagues have recently reported that heart-specific elimination of TRPV2 may be critically detrimental to cardiac structure and function in mice [ 29 ].…”
Section: Discussionsupporting
confidence: 93%
“…First, we wished to analyze whether TRPV2-WT and TRPV2-KO animals demonstrate any differences in cardiac function as previously suggested [ 15 , 16 ]. To this end, TRPV2-WT and KO male mice aged 12–16 weeks (6/arm) were studied by echocardiography.…”
BackgroundWe have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3–5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel.PurposeAssess cardiac function in TRPV2-KO mice compared to TRPV2-WT following AMI and analyze the potential involvement of TRPV2-expressing macrophages in the recovery process.MethodsTRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). In another set of experiments, TRPV2-KO mice induced with AMI, were intravenously (IV) injected with WT or TRPV2-KO peritoneal macrophages in order to directly assess the potential contribution of TRPV2-expressing macrophages to cardiac healing. Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative changes in the ejection fraction (EF) and additional cardiac parameters between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS).ResultsThe in vivo study showed that while EF was significantly decreased in the WT animals between baseline and day 30, EF was only slightly and insignificantly reduced in the KO animals. Likewise LVESD and LVESA were significantly modified exclusively in the WT animals. Moreover, intravenous administration of peritoneal WT macrophages, but not KO macrophages, significantly reduced survival of post-MI TRPV2-KO mice.ConclusionThe data suggest that knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery. TRPV2 may thus represent a novel therapeutic target for treatment of patients undergoing an acute MI.
“…M-mode measurements of the LV end diastolic dimension (LVEDD) and LV end systolic dimension (LVESD), posterior and anterior wall thickness and ejection time, measured at end diastole, were calculated from original tracings by employing a commercially available image analysis system (Freeland Medical, Alpharetta, GA, USA). 41…”
Section: Generation Of Recombinant Proteins and Blot-overlay Assaymentioning
HSPB6/Hsp20 (heat shock protein family B [small] member 6) has emerged as a novel cardioprotector against stress-induced injury. We identified a human mutant of HSPB6 (HSPB6) exclusively present in dilated cardiomyopathy (DCM) patients. Cardiac expression of this mutant in mouse hearts resulted in remodeling and dysfunction, which progressed to heart failure and early death. These detrimental effects were associated with reduced interaction of mutant HSPB6 with BECN1/Beclin 1, leading to BECN1 ubiquitination and its proteosomal degradation. As a result, autophagy flux was substantially inhibited and apoptosis was increased in HSPB6-mutant hearts. In contrast, overexpression of wild-type HSPB6 (HSPB6 WT) not only increased BECN1 levels, but also competitively suppressed binding of BECN1 to BCL2, resulting in stimulated autophagy. Indeed, preinhibition of autophagy attenuated the cardioprotective effects of HSPB6 WT. Taken together, these findings reveal a new regulatory mechanism of HSPB6 in cell survival through its interaction with BECN1. Furthermore, Ser10 appears to be crucial for the protective effects of HSPB6 and transversion of this amino acid to Phe contributes to cardiomyopathy.
“…Although TRPV1 −/− mouse skeletal muscles have never been phenotyped before our investigation, other members of the TRPV family had. Naticchioni et al reported that the contractile function of skeletal muscles was unchanged in TRPV2 null mice [ 45 ]. Similarly, lack of TRPV4 did not cause any alteration of muscular force production or fatigue [ 46 ].…”
The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca2+ that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as a reticular Ca2+-leak channel and several TRPV1 mutations have been associated with two muscle disorders: malignant hyperthermia (MH) and exertional heat stroke (EHS). Although TRPV1−/− mice have been available since the 2000s, TRPV1’s role in muscle physiology has not been thoroughly studied. Therefore, the focus of this work was to characterize the contractile phenotype of skeletal muscles of TRPV1-deficient mice at rest and after four weeks of exercise. As MS and EHS have a higher incidence in men than in women, we also investigated sex-related phenotype differences. Our results indicated that, without exercise, TRPV1−/− mice improved in vivo muscle strength with an impairment of skeletal muscle in vitro twitch features, i.e., delayed contraction and relaxation. Additionally, exercise appeared detrimental to TRPV1−/− slow-twitch muscles, especially in female animals.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.