Effect of Mat Pilates Training on Blood Pressure, Inflammatory, and Oxidative Profiles in Hypertensive Elderly.

To determine the effects of mat Pilates training on blood pressure, inflammatory, and antioxidative markers in hypertensive elderly people, 34 hypertensive subjects aged 60-75 years were randomly divided into a control group (CON; n = 17) and a mat Pilates training group (MP; n = 17). The CON participants conducted normal daily activities and participated in neither organized exercises nor sports training, while those in the MP group received mat Pilates training for 60 min three times/week for 12 weeks. Parameters including blood pressure, cardiovascular function, nitric oxide (NO), tumor necrotic factor-alpha (TNF-α), superoxide dismutase (SOD), and malonaldehyde (MDA) were collected at baseline and the end of 12 weeks. The MP group had significantly decreased blood pressure, improved cardiovascular variables, decreased MDA and TNF-α, and increased NO and SOD compared with the CON group and the pre-training period (p < 0.05). In conclusion, these findings demonstrate the positive effects of 12 weeks of mat Pilates training in terms of reducing blood pressure and increasing blood flow related to improvements in anti-inflammatory and antioxidative markers in hypertensive elderly people. Mat Pilates training might be integrated as an alternative therapeutic exercise modality in clinical practice for hypertensive elderly individuals.

Chondrocyte Thrombomodulin Protects against Osteoarthritis.

Osteoarthritis (OA) is a prevalent form of arthritis that affects over 32.5 million adults worldwide, causing significant cartilage damage and disability. Unfortunately, there are currently no effective treatments for OA, highlighting the need for novel therapeutic approaches. Thrombomodulin (TM), a glycoprotein expressed by chondrocytes and other cell types, has an unknown role in OA. Here, we investigated the function of TM in chondrocytes and OA using various methods, including recombinant TM (rTM), transgenic mice lacking the TM lectin-like domain (TMLeD/LeD), and a microRNA (miRNA) antagomir that increased TM expression. Results showed that chondrocyte-expressed TM and soluble TM [sTM, like recombinant TM domain 1 to 3 (rTMD123)] enhanced cell growth and migration, blocked interleukin-1ß (IL-1ß)-mediated signaling and protected against knee function and bone integrity loss in an anterior cruciate ligament transection (ACLT)-induced mouse model of OA. Conversely, TMLeD/LeD mice exhibited accelerated knee function loss, while treatment with rTMD123 protected against cartilage loss even one-week post-surgery. The administration of an miRNA antagomir (miR-up-TM) also increased TM expression and protected against cartilage damage in the OA model. These findings suggested that chondrocyte TM plays a crucial role in counteracting OA, and miR-up-TM may represent a promising therapeutic approach to protect against cartilage-related disorders.

Branched-Chain Amino Acids Supplementation Does Not Accelerate Recovery after a Change of Direction Sprinting Exercise Protocol.

BCAAs supplementation has been widely used for post-exercise recovery. However, no evidence is currently available to answer the question of whether BCAAs supplementation can attenuate muscle damage and ameliorate recovery after a bout of change of direction (COD) sprinting, which is an exercise motion frequently used during team sport actions. This study aimed to assess the effect of BCAAs supplementation on muscle damage markers, subjective muscle soreness, neuromuscular performance, and the vascular health of collegiate basketball players during a 72 h recovery period after a standardized COD protocol. Participants orally received either BCAAs (0.17 g/kg BCAAs + 0.17 g/kg glucose) or placebo (0.34 g/kg glucose) supplementation before and immediately after a COD exercise protocol in a randomized, crossover, double-blind, and placebo-controlled manner. Creatine kinase increased immediately after exercise and peaked at 24 h, muscle soreness remained elevated until 72 h, whilst arterial stiffness decreased after exercise for both supplemented conditions. A negligibly lower level of interleukin-6 was found in the BCAAs supplemented condition. In conclusion, the results of this study do not support the benefits of BCAAs supplementation on mitigating muscle damage and soreness, neuromuscular performance, and arterial stiffness after COD for basketball players.

Anti-apoptotic and pro-survival effect of exercise training on early aged hypertensive rat cerebral cortex.

The anti-apoptotic and pro-survival effects of exercise training were evaluated on the early aged hypertensive rat cerebral cortex. The brain tissues were analysed from ten sedentary male Wistar Kyoto normotensive rats (WKY), ten sedentary spontaneously 12 month early aged hypertensive rats (SHR), and ten hypertensive rats undergoing treadmill exercise training (60 min/day, 5 days/week) for 12 weeks (SHR-EX). TUNEL-positive apoptotic cells, the expression levels of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) (caspase-independent apoptotic pathway), Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain, active caspase-8 and active caspase-3 (Fas-mediated apoptotic pathways) as well as t-Bid, Bax, Bak, Bad, cytochrome c, active caspase 9 and active caspase-3 (mitochondria-mediated apoptotic pathways) were reduced in SHR-EX compared with SHR. Pro-survival Bcl2, Bcl-xL, p-Bad, 14-3-3, insulin-like growth factor (IGF)-1, pPI3K/PI3K, and pAKT/AKT were significantly increased in SHR-EX compared to those in SHR. Exercise training suppressed neural EndoG/AIF-related caspase-independent, Fas/FasL-mediated caspase-dependent, mitochondria-mediated caspase-dependent apoptotic pathways as well as enhanced Bcl-2 family-related and IGF-1-related pro-survival pathways in the early aged hypertensive cerebral cortex. These findings indicated new therapeutic effects of exercise training on preventing early aged hypertension-induced neural apoptosis in cerebral cortex.

Exercise training attenuates cardiac inflammation and fibrosis in hypertensive ovariectomized rats.

This study investigated the effects of exercise training on cardiac inflammatory and cardiac fibrotic pathways in female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive group (SHR-S), a sedentary hypertensive ovariectomized group (SHR-O), or a hypertensive ovariectomized group with treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk. Normotensive female Wistar-Kyoto rats (WKY) served as controls. SOD and catalase (CAT) activities were significantly increased in the SHR-OT group, when compared with the SHR-S or SHR-O groups. The protein levels of estrogen receptor (ER)-α and ER-ß became decreased in the SHR-O group, when compared with the WKY or SHR-S groups, but were not changed in the SHR-OT group. The protein level of the angiotensin II type I receptor (AT1R) was increased in the SHR-S group but did not further change in the SHR-O group, whereas it was decreased in the SHR-OT group. The inflammatory-related protein levels of TNF-α, p-NF-κB, cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6, as well as the fibrotic-related protein levels of transforming growth factor-ß (TGF-ß), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I were increased in the SHR-S group and increased further in the SHR-O group, whereas they were decreased in the SHR-OT group. The coexistence of hypertension and ovariectomy additively increased cardiac inflammatory and fibrotic pathways partially through hypertension-enhanced AT1R and ovariectomy-depressed estrogen receptors. Exercise training appeared to suppress hypertensive ovariectomized heart-induced inflammatory and fibrotic pathways possibly through decreasing AT1R but not through estrogen receptors.NEW & NOTEWORTHY The coexistence of hypertension and ovariectomy appeared to increase cardiac inflammatory and fibrotic pathways likely through hypertension-enhanced angiotensin II type I receptor and ovariectomy-depressed estrogen receptors. Exercise training on a treadmill could prevent hypertensive ovariectomized heart-induced cardiac inflammation and fibrosis via an inflammatory pathway [TNF-α, p-IKK-α/ß, p-NF-κB, cyclooxygenase 2 (COX-2), iNOS, and IL-6] and fibrotic pathway [transforming growth factor-ß (TGF-ß), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I] possibly through decreasing angiotensin II type I receptor but not through estrogen receptors.

Antiapoptotic and mitochondrial biogenetic effects of exercise training on ovariectomized hypertensive rat hearts.

This study was to investigate the effects of exercise training on antiapoptotic pathways and mitochondrial biogenesis in ovariectomized hypertensive rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive (SHR-S), a sedentary hypertensive ovariectomized (SHR-O), and hypertensive ovariectomized rats that underwent treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk, along with normotensive Wistar Kyoto rats (WKY). When compared with the WKY group, the SHR-S group exhibited decreased protein levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial OPA-1 (mitochondrial biogenesis) and decreased further in the SHR-O group. The protein levels of p-PI3K, p-Akt, Bcl-2, Bcl-xL (prosurvival pathways), and the protein levels of PGC-1α and mitochondrial OPA1 (mitochondrial biogenesis) were increased in the SHR-OT group, but estrogen receptor (ER)α and ERß were not changed when compared with the SHR-O group. The protein levels of t-Bid, Bad, Bax, cytosolic cytochrome c, activated caspase 9, and activated caspase 3 (mitochondria-dependent apoptotic pathways), as well as Fas ligand, TNF-α, Fas receptors, Fas-associated death domain, activated caspase 8 (Fas receptor-dependent apoptotic pathways) were decreased in the SHR-OT group, when compared with the SHR-O group. Exercise training protection on the coexistence of hypertension and ovariectomy-induced cardiac mitochondria-dependent and Fas receptor-dependent apoptotic pathways by enhancing the Bcl2-related and mitochondrial biogenetic prosurvival pathways might provide a new therapeutic effect on cardiac protection in oophorectomized early postmenopausal hypertensive women. NEW & NOTEWORTHY Widely dispersed cardiac apoptosis was found in the coexistence of hypertension and ovariectomy. Exercise training on a treadmill could prevent ovariectomized hypertension-induced widely dispersed cardiac apoptosis via mitochondria-dependent apoptotic pathway (t-Bid, Bad, Bax, cytosolic cytochrome c, activated caspase 9, and activated caspase 3) and Fas receptor-dependent apoptotic pathway (Fas ligand, tumor necrosis factor-α, Fas receptors, Fas-associated death domain, activated caspase 8, and activated caspase 3) through enhancing the Bcl2-related (p-PI3K, p-Akt, Bcl-2, Bcl-xL) and mitochondrial biogenetic (PGC-1α and mitochondrial optic atrophy 1) prosurvival pathways.

Twelve-Week Protocatechuic Acid Administration Improves Insulin-Induced and Insulin-Like Growth Factor-1-Induced Vasorelaxation and Antioxidant Activities in Aging Spontaneously Hypertensive Rats.

Protocatechuic acid (PCA), a strong antioxidant, has been reported for its cardiovascular-protective effects. This study aimed to investigate the effects of PCA administration on vascular endothelial function, mediated by insulin and insulin-like growth factor-1 (IGF-1), and antioxidant activities in aging hypertension. Thirty-six-week-old male aging spontaneously hypertensive rats were randomly divided into vehicle control (SHR) and PCA (SHR+PCA) groups, while age-matched Wistar⁻Kyoto rats (WKY) served as the normotensive vehicle control group. The oral PCA (200 mg/kg/day) was administered daily for a total of 12 weeks. When the rats reached the age of 48 weeks, the rat aortas were isolated for the evaluation of vascular reactivity and Western blotting. Also, nitric oxide (NO) production and antioxidant activities were examined among the three groups. The results showed that, when compared with the SHR group, the insulin-induced and IGF-1-induced vasorelaxation were significantly improved in the SHR+PCA group. There was no significant difference in the endothelium-denuded vessels among the three groups. After the pre-incubation of phosphatidylinositol 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the vasorelaxation was abolished and comparable among the three groups. The protein levels of insulin receptors, IGF-1 receptors, phospho-protein kinase B (p-Akt)/Akt, and phospho-endothelial NOS (p-eNOS)/eNOS in aortic tissues were significantly enhanced in the SHR+PCA group when compared with the SHR group. Moreover, significant improvements of nitrate/nitrite concentration and antioxidant activities, including superoxide dismutase, catalase, and total antioxidants, were also found in the SHR+PCA group. In conclusion, the 12 weeks of PCA administration remarkably improved the endothelium-dependent vasorelaxation induced by insulin and IGF-1 in aging hypertension through enhancing the PI3K⁻NOS⁻NO pathway. Furthermore, the enhanced antioxidant activities partly contributed to the improved vasorelaxation.

Combined effects of 17ß-estradiol and exercise training on cardiac apoptosis in ovariectomized rats.

BACKGROUND: The purpose of this study was to investigate the combined 17ß-estradiol (E2) and exercise training on cardiac pro-survival and anti-apoptotic pathways in ovariectomized rats. METHODS: Fifty-six female Sprague-Dawley rats were divided into a sham-operated (Sham), a bilaterally ovariectomized (OVX), an OVX treated with E2 (OVX-E2; 10µg/kg/day), and an OVX with E2 and treadmill exercise training (OVX-E2-EX; 60 min/day, 5 days/week) for 10 weeks. Following 10 weeks of exercise training, rat hearts were isolated for the evaluation of Histopathological analysis, TUNEL assay, and Western blotting. RESULTS: The protein levels of estrogen receptor α (ERα), estrogen receptor ß (ERß), insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), phospho-phosphatidylinositol 3-kinase (p-PI3K) (estrogen receptors/IGF-1-related survival pathway) were significantly increased in either the OVX-E2 or OVX-E2-EX group when compared with the OVX group. The protein levels of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xL) and phosphorylated-Bad (p-Bad) (Bcl-2 family survival pathway) were significantly increased in the OVX-E2-EX group when compared with the OVX group. Only the p-Bad was significantly increased in the OVX-E2 group when compared with the OVX group. The protein levels of truncation of Bid (t-Bid), Bcl-2-associated death promotor (Bad), Bcl-2-associated X protein (Bax), Cytochrome c, caspases-9, and caspases-3 (mitochondria-dependent apoptotic pathway), as well as the protein levels of tumor necrosis factor-α (TNF-α), Fas ligand, Fas receptors, Fas-associated death domain (FADD), activated caspase-8 and activated caspase-3 (Fas receptor-dependent apoptotic pathway) were significantly decreased in either the OVX-E2 or OVX-E2-EX group when compared with the OVX group. Furthermore, when compared with the OVX-E2 group, the protein levels of ERß, IGF-1, IGF-1R, Bcl-2 and Bcl-xL were further enhanced in the OVX-E2-EX group as well as the protein levels of Cytochrome c, Fas receptors, FADD, activated caspase-8, activated caspase-9 and activated caspase-3 were further decreased in the OVX-EX-E2 group. CONCLUSIONS: Combined E2 and exercise training exhibited a positive effect of protection on ovariectomy-induced cardiac apoptosis by enhancing ERß-related survival pathways, which might provide a more effective therapeutic effect on cardiac protection in bilaterally oophorectomized or menopausal women than E2 treatment only.

Anti-Renal Fibrotic Effect of Exercise Training in Hypertension.

The purpose of this study was to evaluate the effects of exercise training on renal fibrosis in hypertensive rats. Masson's trichrome staining and Western blotting were performed on the excised renal cortex from sixteen male spontaneously hypertensive rats (SHR), which were randomly divided into either a sedentary hypertensive group (SHR) or exercise hypertensive group (SHR-EX, running on an exercise treadmill for 60 min/day, 5 sessions/week, for 12 weeks), and from eight male Wistar-Kyoto rats which served as a sedentary normotensive group (WKY). The systolic blood pressure (SBP) and renal fibrosis in hypertensive rats improved after exercise training. The inflammatory-related protein levels of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), as well as the fibrotic-related protein levels of transforming growth factor-beta (TGF-ß), phospho-Smad2/3 (p-Smad2/3), connective tissue growth factor (CTGF), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-2 (MMP-2) were decreased in the SHR-EX group when compared with the SHR group. Exercise training suppressed the hypertension-induced renal cortical inflammatory and fibrotic pathways in hypertensive rat models. These findings might indicate a new therapeutic effect for exercise training to prevent renal fibrosis in hypertensive nephropathy.

The Coexistence of Hypertension and Ovariectomy Additively Increases Cardiac Apoptosis.

To investigate whether the coexistence of hypertension and ovariectomy will increase cardiac Fas receptor and mitochondrial-dependent apoptotic pathways, histopathological analysis, the TUNEL assay and Western blotting were performed on the excised hearts from three groups of female spontaneously hypertensive rats (SHR), which were divided into a sham-operated group (SHR-Sham), bilaterally ovariectomized group (SHR-OVX) and normotensive Wistar Kyoto rats (WKY). Compared with the WKY group, the SHR-Sham group exhibited decreased protein levels of ERα, ERß, p-Akt/Akt, Bcl-2, Bcl-xL and p-Bad and decreased further in the SHR-OVX group, as well as protein levels of t-Bid, Bak, Bad, Bax, cytochrome c, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptosis) increased in the SHR-Sham group and increased further in the SHR-OVX group. Compared with the WKY group, protein levels of Fas ligand, TNF-α, Fas death receptors, TNFR1, FADD and activated caspase-8 (Fas receptor-dependent apoptosis) increased in the SHR-Sham group, but did not increase in the SHR-OVX group, except Fas ligand and TNF-α. The coexistence of hypertension and ovariectomy attenuated the estrogen receptor survival pathway and appeared to additively increase the cardiac mitochondria-dependent, but not the Fas receptor-dependent apoptosis pathway, which might provide one possible mechanism for the development of cardiac abnormalities in hypertensive postmenopausal women.

Myeloid thrombomodulin lectin-like domain inhibits osteoclastogenesis and inflammatory bone loss.

Osteoclastogenesis is an essential process during bone metabolism which can also be promoted by inflammatory signals. Thrombomodulin (TM), a transmembrane glycoprotein, exerts anti-inflammatory activities such as neutralization of proinflammatory high-mobility group box 1 (HMGB1) through TM lectin-like domain. This study aimed to identify the role of myeloid TM (i.e., endogenous TM expression on the myeloid lineage) in osteoclastogenesis and inflammatory bone loss. Using human peripheral blood mononuclear cells and mouse bone marrow-derived macrophages, we observed that the protein levels of TM were dramatically reduced as these cells differentiated into osteoclasts. In addition, osteoclastogenesis and extracellular HMGB1 accumulation were enhanced in primary cultured monocytes from myeloid-specific TM-deficient mice (LysMcre/TM(flox/flox)) and from TM lectin-like domain deleted mice (TM(LeD/LeD)) compared with their respective controls. Micro-computerized tomography scans showed that ovariectomy-induced bone loss was more pronounced in TM(LeD/LeD) mice compared with controls. Finally, the inhibiting effects of recombinant TM lectin-like domain (rTMD1) on bone resorption in vitro, and bone loss in both the ovariectomized model and collagen antibody-induced arthritis model has been detected. These findings suggested that the myeloid TM lectin-like domain may inhibit osteoclastogenesis by reducing HMGB1 signaling, and rTMD1 may hold therapeutic potential for inflammatory bone loss.

Antiapoptotic effect of exercise training on ovariectomized rat hearts.

The purpose of this study was to evaluate the effects of exercise training on cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats, which were divided into a sham-operated group, a bilaterally ovariectomized group (OVX), and a bilaterally ovariectomized group that underwent treadmill running exercise for 60 min/day, 5 sessions/wk, for 10 wk (OVX-EX). The abnormal myocardial architecture, cardiac trichome-stained fibrosis and cardiac TUNEL-positive apoptotic cells in ovariectomized rats improved after exercise training. The protein levels of tumor necrosis factor-α, tumor necrosis factor receptor 1, Fas ligand, Fas receptors, Fas-associated death domain, activated caspase-8 and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid, Bad, Bak, Bax, cytosolic cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the OVX-EX group compared with the OVX group. Exercise training suppressed ovariectomy-induced cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rat models. These findings might indicate a new therapeutic effect for exercise training to prevent cardiac apoptosis in menopausal or bilaterally oophorectomized women.

Cardiac hypertrophy-related pathways in obesity.

Obesity is often associated with the development of cardiac hypertrophy but the hypertrophy-related pathways in obesity remain unknown. The purpose of this study was to evaluate cardiac hypertrophy-related markers, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), tumor necrosis factor-alpha (TNFα) and hypertrophy-related pathways, interleukin (IL)-6-STAT3, IL-6-MEK5-ERK5 and calcineurin-nuclear factor of activated T-cells (NFAT)3 in the excised hearts from obese rats. Twelve obese Zucker rats were studied at 5-6 months of age and twelve age-matched lean Zucker rats served as the control group. The cardiac characteristics, myocardial architecture, ANP, BNP, TNFα levels, IL-6, STAT3, p-STAT3, MEK5, ERK-5, p-ERK-5, calcineurin and NFAT3 in the left ventricle from the rats were measured by heart weight index, echocardiography, vertical cross section, histological analysis, reverse transcription polymerase chain reaction and western blotting. Compared with the lean control, the whole heart weight, the left ventricule weight, the ratio of the whole heart weight to tibia length, echocardiographic interventricular septum, left ventricular posterior wall thickness, myocardial morphological changes and systolic blood pressure were found to increase in the obese rats. The protein levels of ANP, BNP, TNFα, IL-6, STAT3, p-STAT3, MEK-5, ERK-5, p-ERK 5, calcineurin and NFAT3 were also significantly increased in the hearts of the obese rats. The results showed that the hypertrophy-related markers, ANP, BNP and TNFα, the hypertrophy-related pathways IL-6-STAT3 and IL-6-MEK5-ERK5, and the calcineurin-NFAT3 hypertrophy-related pathways were more active in obese Zucker rats, which may provide possible hypertrophic mechanisms for developing cardiac hypertrophy and pathological changes in obesity.

Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats.

BACKGROUND: Increased myocyte apoptosis in diabetic hearts has been previously reported. The purpose of this study was to evaluate the effects of exercise training on cardiac survival pathways in streptozotocin (STZ)-induced diabetic rats. METHODS: Forty-eight male Wistar rats were randomly divided into control group (Control), STZ-induced (65 mg/kg, i.p.) diabetes (DM), and DM rats with moderate aerobic exercise training (DM-EX) on a treadmill 60 min/day, 5 days/week, for 10 weeks. Histopathological analysis, positive TUNEL assays and Western blotting were performed on the excised cardiac left ventricles from all three groups. RESULTS: The components of cardiac survival pathway (insulin-like growth factor I (IGFI), IGFI-receptor (IGFI-R), phosphatidylinositol 3'-kinase (PI3K), and Akt) and the pro-survival Bcl-2 family proteins (Bcl-2, Bcl-xL, and p-BAD) were all significantly decreased in the DM group compared with the Control group whereas they were increased in the DM-EX group. In addition, the abnormal myocardial architecture, enlarged interstitial space and increased cardiac TUNEL-positive apoptotic cells were observed in the DM group, but they were reduced in the DM-EX group. The apoptotic key component, caspase-3, was significantly increased in the DM group relative to the Control group whereas it was decreased in the DM-EX group. CONCLUSIONS: Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways, which provides one of the new beneficial effects for exercise training in diabetes.

Anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts.

BACKGROUND: Activated cardiac apoptosis was found in hearts from hypertensive animals, but little information regarding the effects of exercise training on cardiac apoptosis in hypertension is available. The purpose of this study was to evaluate the anti-apoptotic and pro-survival effects of exercise training on hypertensive hearts. METHODS: 28 spontaneously hypertensive rats were divided into sedentary group (SHR) or underwent running exercise on treadmill for 1 h/day, 5 sessions/wk, for 12 wk (SHR-EX). Fourteen age-matched Wistar Kyoto rats served as a sedentary normotensive group (WKY). After exercise training or sedentary status, the excised hearts were measured by hemotoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) assay, and Western blotting. RESULTS: Fewer TUNEL-positive apoptotic cells were in SHR-EX groups than those in SHR. Protein levels of Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathways), as well as Bid, t-Bid, Bad, p-Bad, Bak, cytochrome c, activated caspase 9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the SHR-EX group compared with the SHR group. Protein levels of IGF-1, IGF-1R, p-PI3K, p-Akt, p-Bad, and Bcl2 (cardiac pro-survival pathway) become more activated in SHR-EX groups than SHR and WKY. CONCLUSIONS: Exercise training prevented hypertension-enhanced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways and enhanced cardiac pro-survival pathway in rat models. Our findings demonstrate new therapeutic effects of exercise training on hypertensive hearts for preventing apoptosis and enhancing survival.

Effects of 17beta-estradiol on cardiac apoptosis in ovariectomized rats.

OBJECTIVES: Cardiac apoptosis was found in ovariectomized rats without ischemia. Limited information regarding the protective effects of 17beta-estradiol (E2) on cardiac Fas-dependent and mitochondria-dependent apoptotic pathways after post-menopause or bilateral oophorectomy in women was available. METHODS: Forty-eight female Wistar rats at 6-7 months of age were divided into sham-operated group (Sham, n = 16) and bilateral ovariectomized group (n = 32). After 4 weeks of operation, rats in ovariectomized group were injected intraperitoneally with either saline (OVX, n = 16) or 10 microg/kg/day 17beta-estradiol (E2) for 10 weeks (OVX-E2, n = 16). The excised hearts were measured by Hematoxylin-eosin staining, DAPI staining, positive TUNEL assays, and Western Blotting. RESULTS: 17beta-estradiol (E2) decreased OVX-induced cardiac widely dispersed TUNEL-positive apoptotic cells. 17beta-estradiol (E2) decreased OVX-induced TNF-alpha, Fas ligand (Fas L), Fas death receptors (Fas), Fas-associated death domain (FADD), activated caspase 8, and activated caspase 3 (Fas pathways). 17beta-estradiol (E2) decreased OVX-induced proapoptotic t-Bid, Bax, Bax-to-Bcl2 ratio, Bax-to-BclXL ratio, activated caspase 9, and activated caspase 3 as well as increased anti-apoptotic Bcl2 and Bcl-XL relative to OVX (mitochondria pathway). CONCLUSIONS: Our findings suggest that chronic 17beta-estradiol (E2) treatment can prevent ovariectomy-induced cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in rat models. The findings may provide one of possible mechenisms of 17beta-estradiol (E2) for potentially preventing cardiac apoptosis after bilateral ovariectomy or menopause.

Cardiac Fas-dependent and mitochondria-dependent apoptosis in ovariectomized rats.

BACKGROUND: Very limited information has been published regarding cardiac apoptosis in menopausal women or in those after bilateral oophorectomy. The purpose of this study was to evaluate whether cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways are activated in ovariectomized rats. METHODS: Thirty-two female Wistar rats at 6-7 months of age were randomly divided into sham-operated group (Sham) and bilateral ovariectomized group (OVX). Two months after the operation, the cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from rats were measured by histopathological analysis, Western blotting and reverse transcription polymerase chain reaction (RT-PCR), and positive TUNEL assays. RESULTS: The whole heart weight, the left ventricular weight, the ratios of whole heart weight to tibia length, and the ratios of left ventricle to tibia length were significantly increased in OVX relative to Sham. Abnormal myocardial architecture, enlarged interstitial spaces, more minor cardiac fibrosis, and more cardiac TUNEL-positive apoptotic cells were observed in OVX. The key components of Fas-dependent apoptosis (TNF-alpha, Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase 8, and activated caspase 3) and key components of mitochondria-dependent apoptosis (Bad, Bax, Bax-to-Bcl2 ratio, cytosolic cytochrome c, activated caspase 9, and activated caspase 3) were significantly increased in OVX hearts. CONCLUSIONS: The absence of female ovaries will activate the cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which might provide one of possible mechanism for developing heart failure in post-menopause women.

Effects of short- and long-term hypobaric hypoxia on Bcl2 family in rat heart.

BACKGROUND: Controversial effects of intermittent hypobaric hypoxia such as cardiac damage or cardiac protection are still mysterious. It is unclear if short-term and long-term intermittent hypobaric hypoxic challenges exert different effects on cytochrome c oxidase and Bcl-2 family in rat heart. METHODS: Sixty Sprague-Dawley rats were randomized assigned into two groups: first, short-term intermittent hypobaric hypoxia (STIHH)-normobaric normoxia (n=10), hypobaric hypoxia (380 mmHg, 12% O2, 8 hr/day) for 1 day (n=10), and for 4 days (n=10) and second, long-term intermittent hypobaric hypoxia (LTIHH)-normobaric normoxia (n=10), hypobaric hypoxia for 1 week (n=10) and 2 weeks (n=10). After STIHH or LTIHH challenge, myocardial morphology, cytochrome c oxidase and pro-apoptotic Bcl-2 family in the excised left ventricle were determined by histological analysis, Western blotting, and RT-PCR. RESULTS: Increased wall thickness and abnormal myocardial architecture were observed after LTIHH. Cytochrome c oxidase and anti-apoptotic Bcl-2 protein were significantly increased after STIHH, but were decreased after LTIHH. Pro-apoptotic BNIP3 and Bad proteins were significantly decreased after STIHH but increased after LTIHH. CONCLUSIONS: STIHH appeared to exert protective effects on hearts whereas LTIHH appeared to exert deleterious effects, which imply that deleterious or advantageous effect of cardiac adaptation after intermittent hypobaric hypoxia is tightly time-course dependent.