Corrigendum: 9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice

Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.

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PKCβ inhibition with ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfuntion in rats with streptozotocin-induced diabetes

Clinical Science ◽

10.1042/cs20110176 ◽

2011 ◽

Vol 122 (4) ◽

pp. 161-173 ◽

Cited By ~ 49

Author(s):

Yanan Liu ◽

Shaoqing Lei ◽

Xia Gao ◽

Xiaowen Mao ◽

Tingting Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Nadph Oxidase ◽

Myocardial Hypertrophy ◽

Weight Ratio ◽

Cardiovascular Complications ◽

Diabetic Rats ◽

Left Ventricular ◽

Control Group ◽

Cross Sectional

Oxidative stress plays critical roles in the development of diabetic cardiovascular complications, including myocardial hypertrophy. The β isoform of PKC (protein kinase C) is preferentially overexpressed in the myocardium of diabetic subjects accompanied with increased activation of the pro-oxidant enzyme NADPH oxidase, which may exacerbate oxidative stress. We hypothesized that myocardial PKCβ is a major upstream mediator of oxidative stress in diabetes and that PKCβ inhibition can attenuate myocardial hypertrophy and dysfunction. Control or streptozotocin-induced diabetic rats were treated with the selective PKCβ inhibitor RBX (ruboxistaurin; 1 mg/kg of body weight per day) or the antioxidant NAC (N-acetylcysteine) for 4 weeks. LV (left ventricular) dimensions and functions were detected by echocardiography. 15-F2t-isoprostane (a specific index of oxidative stress) and myocardial activities of superoxide dismutase as well as protein levels of NADPH oxidase were assessed by immunoassay or Western blotting. Echocardiography revealed that the LV mass/body weight ratio was significantly increased in diabetic rats (P<0.01 compared with the control group) in parallel with the impaired LV relaxation. A significant increase in cardiomyocyte cross-sectional area was observed in diabetic rats accompanied by an increased production of O2− (superoxide anion) and 15-F2t-isoprostane (all P<0.05 compared with the control group). RBX normalized these changes with concomitant inhibition of PKCβ2 activation and prevention of NADPH oxidase subunit p67phox membrane translocation and p22phox overexpression. The effects of RBX were comparable with that of NAC, except that NAC was inferior to RBX in attenuating cardiac dysfunction. It is concluded that RBX can ameliorate myocardial hypertrophy and dysfunction in diabetes, which may represent a novel therapy in the prevention of diabetic cardiovascular complications.

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Role of TLR4/MyD88 Signaling Pathway in the Occurrence and Development of Uremia-Induced Myocardial Hypertrophy and Possible Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/7883643 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Huiping Zhu ◽

Liutong Pan ◽

Yuanting Dai ◽

Dan Zheng ◽

Shasha Cai

Keyword(s):

Kidney Disease ◽

Signaling Pathway ◽

Myocardial Hypertrophy ◽

Kidney Tissue ◽

Cardiorenal Syndrome ◽

Cardiovascular Complications ◽

Compensatory Hypertrophy ◽

Myocardial Tissue ◽

Renal Tubules ◽

Myd88 Signaling

The morbidity and mortality of cardiovascular disease (CVD) are relatively high. Studies have shown that most patients with chronic kidney disease (CKD) die from cardiovascular complications. Clinically, the pathophysiological state in which heart disease and kidney disease are causal and influence each other is called cardiorenal syndrome (CRS). Myocardial hypertrophy is the key stage of the heart structure changing from reversible to irreversible. It is an important pathophysiological basis for heart failure. Therefore, this study intends to start with the end-stage uremic phase of CKD to construct an animal model of uremia in rats to study the relationship between uremia, TLR4/MyD88 signaling pathway, and myocardial hypertrophy. The results showed that the uremic rats showed slow weight gain and were thinner. At 12 weeks (w), the serum creatinine and urea nitrogen of the uremic rats increased, and the global hypertrophy index increased. Detecting the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (MyD88) in blood samples of rats, we found that the expression of TLR4 and MyD88 increased at 12 w in the uremia group; pathological observation showed that at 4 weeks of uremia model rats, renal tissue compensatory hypertrophy, renal fibrous membrane proliferation, renal parenchyma atrophy, a large number of fibrous proliferation and inflammatory cell infiltration in the interstitium, and protein casts in the renal tubules were observed. Myocardial cells were obviously hypertrophy and disordered. At 12 w, renal tubules were obviously expanded, the epithelium was flat, the brush border disappeared, and the interstitial fibrous connective tissue of the myocardial tissue was proliferated. The detection of TLR4 and MyD88 in kidney tissue and myocardial tissue revealed that the positive expression of TLR4 and MyD88 gradually increased over time. Therefore, the final result of the study is that uremia can gradually lead to myocardial hypertrophy and TLR4 and MyD88 are highly expressed in serum, kidney, and myocardial tissues of uremic rats, suggesting that TLR4 and MyD88 may be related to the degree of uremic disease and the myocardium caused by it. Hypertrophy is related.

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The MAP4 Projection Domain Accelerates Hypoxia-Induced Mitophagy Disruption through LIR Motif in Cardiomyocytes

10.21203/rs.3.rs-1014224/v1 ◽

2021 ◽

Author(s):

Yuesheng Huang ◽

Yanhai Feng ◽

Qiong Zhang ◽

Lingfei Li ◽

Junhui Zhang ◽

...

Keyword(s):

Heart Failure ◽

Myocardial Hypertrophy ◽

Myocardial Damage ◽

Autophagic Flux ◽

Ischemic Heart Failure ◽

Detailed Mechanism ◽

Mitochondrial Translocation ◽

Promising Therapeutic Target ◽

Projection Domain ◽

Lir Motif

Abstract Previously, we and other investigators have demonstrated that phosphorylated microtubule-associated protein 4 (p-MAP4) impacts myocardial hypertrophy and ischemic heart failure. However, the detailed mechanism behind this remains under elucidated. Published studies have suggested that impaired mitophagy contributes to hypoxia-induced myocardial damage, hence the involvement of p-MAP4 in mitophagy in cardiomyocytes was investigated. The results herein revealed that there was increased degradation of mitochondria, accumulated mitophagosomes and disrupted autophagic flux in both neonatal and adult ones of MAP4-knockin (KI) mice. This indicated that p-MAP4 persistently degraded mitochondria through activating mitophagy. Next, Tom70 was found as the importer of p-MAP4 in the context of mitochondrial translocation. And, the LC3-interacting region (LIR) motif (47–50aa) caused p-MAP4-induced mitochondrial engulfment, and the ubiquitin-interacting motif (UIM) domain determined the characteristics of p-MAP4-induced mitophagosomes, which were structure and membrane potential-independent. Moreover, p-MAP4 enhanced hypoxia-induced mitophagic flux impairment, and p-MAP4 LIR (47–50aa) mutation decreased hypoxia-induced autophagy both in MAP4 knockout and wildtype cardiomyocytes. Overall, this study identified that p-MAP4 as a novel mediator and cargo receptor in mitophagy, and that the degradation of the MAP4 PJ domain as a promising therapeutic target for improving the cardiac function of hypoxia-related heart failure or cardiac remodelling.

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183 Role of the ubiquitin-proteasome system in the development of myocardial hypertrophy

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(03)90110-x ◽

2003 ◽

Vol 2 (1) ◽

pp. 36

Author(s):

K STANGL ◽

H DREGER ◽

V STANGL ◽

G BAUMANN ◽

S MEINERS

Keyword(s):

Myocardial Hypertrophy ◽

Ubiquitin Proteasome System ◽

Ubiquitin Proteasome

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Cardiovascular complications during medication adjustment for the diagnosis of primary aldosteronism

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0034-1372085 ◽

2014 ◽

Vol 122 (03) ◽

Author(s):

M Shlyakhova ◽

JW Lenders ◽

J Deinum

Keyword(s):

Primary Aldosteronism ◽

Cardiovascular Complications ◽

Medication Adjustment

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Update CACOCA Trial (cardiovascular complications of cancer treatment)

Pneumologie ◽

10.1055/s-0034-1375924 ◽

2014 ◽

Vol 68 (05) ◽

Author(s):

F Kocher ◽

B Föger ◽

M Fiegl ◽

M Fridrik ◽

G Gastl ◽

...

Keyword(s):

Cancer Treatment ◽

Cardiovascular Complications

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Mechanisms for Cardiovascular Complications of Diabetes - Implications for Personalized Therapy

Endocrine Abstracts ◽

10.1530/endoabs.63.s30.1 ◽

2019 ◽

Author(s):

E Dale Abel

Keyword(s):

Cardiovascular Complications ◽

Personalized Therapy ◽

Complications Of Diabetes

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Pregnancy-Related Cardiovascular Complications: Case Presentation and Review of Literature

The Heart Surgery Forum ◽

10.1532/hsf.1654 ◽

2016 ◽

Vol 19 (5) ◽

pp. E248-E254 ◽

Cited By ~ 3

Author(s):

Hasan Baki Altinsoy ◽

Ozkan Alatas ◽

Salih Colak ◽

Hakan Atalay ◽

Omer Faruk Dogan

Keyword(s):

Cardiac Surgery ◽

Cesarean Section ◽

Pregnant Women ◽

Median Time ◽

Artery Bypass ◽

Prosthetic Heart Valve ◽

Cardiovascular Complications ◽

Time To Diagnosis ◽

Valve Thrombosis ◽

Placental Blood

Background: Cardiovascular complications that can cause severe catastrophic outcomes for both the mother and the fetus are rarely seen during pregnancy. Time to diagnosis is often delayed by a low degree of suspicion and atypical presentation. We report surgical strategies in three pregnant women with cardiovascular complications. Methods: A retrospective search from 2009 to 2016 identified three pregnant women who underwent urgent cardiac surgery. We used extracorporeal circulation (ECC) without cesarean section with careful follow-up of the fetuses during the perioperative and postoperative period. We used levosimendan as a potent inodilator in all patients to increase feto-placental blood flow and fetal heart rhythm.Results: Median time to diagnosis was 23.8 h (range 11.7-120 h) and median time from diagnosis to arrival in the operating theater was 9.8 h (range 7.4-19.8 h). One patient with prosthetic heart valve thrombosis underwent concomitant cesarean section prior to cardiac surgery. In a young pregnant woman who had spontaneous dissection of the left anterior descending artery, on-pump beating heart coronary artery bypass grafting was performed without cross clamping. Two and three months after surgery, cesarean sections were performed without any complication in two pregnant women.Conclusion: Because unusual cardiovascular complications are the main cause of maternal and/or fetus death during pregnancy, prompt and exact diagnosis is very important. Life-saving surgical strategy with the help of appropriate teams are necessary to optimize outcome for both mother and baby.

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