scholarly journals Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction

2014 ◽  
Vol 307 (5) ◽  
pp. H741-H751 ◽  
Author(s):  
Hongmei Peng ◽  
Jiang Xu ◽  
Xiao-Ping Yang ◽  
Xiangguo Dai ◽  
Edward L. Peterson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cell Survival ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cardiac Rupture ◽  
Gelatinolytic Activity ◽  
P53 Expression

Thymosin-β4 (Tβ4) promotes cell survival, angiogenesis, and tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces the incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg·kg−1·day−1 ip via osmotic minipump) for 7 days or 5 wk. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis, and interstitial collagen fraction histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of ICAM-1 and p53 by immunoblot analysis. Tβ4 reduced cardiac rupture that was associated with a decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, a decrease in gelatinolytic activity and ICAM-1 and p53 expression, and an increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, markedly reduced interstitial collagen fraction, and increased capillary density. In a murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus, the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.

scholarly journals N-acetyl-seryl-aspartyl-lysyl-proline treatment protects heart against excessive myocardial injury and heart failure in mice

2019 ◽  
Vol 97 (8) ◽  
pp. 753-765
Author(s):  
Hongmei Peng ◽  
Jiang Xu ◽  
Xiao-Ping Yang ◽  
Kamal M. Kassem ◽  
Imane A. Rhaleb ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Capillary Density ◽  
Cardiac Rupture ◽  
Gelatinolytic Activity ◽  
Intercellular Adhesion Molecule ◽  
P53 Expression ◽  
And Function

Myocardial infarction (MI) in mice results in cardiac rupture at 4–7 days after MI, whereas cardiac fibrosis and dysfunction occur later. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory, anti-fibrotic, and pro-angiogenic properties. We hypothesized that Ac-SDKP reduces cardiac rupture and adverse cardiac remodeling, and improves function by promoting angiogenesis and inhibiting detrimental reactive fibrosis and inflammation after MI. C57BL/6J mice were subjected to MI and treated with Ac-SDKP (1.6 mg/kg per day) for 1 or 5 weeks. We analyzed (1) intercellular adhesion molecule-1 (ICAM-1) expression; (2) inflammatory cell infiltration and angiogenesis; (3) gelatinolytic activity; (4) incidence of cardiac rupture; (5) p53, the endoplasmic reticulum stress marker CCAAT/enhancer binding protein homology protein (CHOP), and cardiomyocyte apoptosis; (6) sarcoplasmic reticulum Ca2+ ATPase (SERCA2) expression; (7) interstitial collagen fraction and capillary density; and (8) cardiac remodeling and function. Acutely, Ac-SDKP reduced cardiac rupture, decreased ICAM-1 expression and the number of infiltrating macrophages, decreased gelatinolytic activity, p53 expression, and myocyte apoptosis, but increased capillary density in the infarction border. Chronically, Ac-SDKP improved cardiac structures and function, reduced CHOP expression and interstitial collagen fraction, and preserved myocardium SERCA2 expression. Thus, Ac-SDKP decreased cardiac rupture, ameliorated adverse cardiac remodeling, and improved cardiac function after MI, likely through preserved SERCA2 expression and inhibition of endoplasmic reticulum stress.

Abstract 13810: TT-00920, a Clinical Stage Novel Phosphodiesterase 9 Inhibitor, Protects Against Heart Failure in a Rat Model of Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zejuan Sheng ◽  
Xiaoyan Qiang ◽  
Guoyu Li ◽  
Huimin Wang ◽  
Wenxin Dong ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Rat Model ◽  
Cardiac Fibrosis ◽  
Clinical Stage ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
Therapeutic Effects ◽  
Dependent Manner

Introduction: Phosphodiesterase 9 (PDE9) controls natriuretic-peptide-stimulated cyclic guanosine monophosphate in cardiac myocytes and is stongly upregulated in human heart failure, suggesting its potential as a promising therapeutic target in heart failure. Here we investigated the potential effects of TT-00920, a clinical stage novel and highly selective PDE9 inhibitor, on heart failure in a rat model of myocardial infarction. Methods: Myocardial infarction was induced by left anterior descending coronary artery (LAD) ligation in male Sprague Dawley rats. After 4-week treatment of vehicle, LCZ696, TT-00920, or TT-00920/Valsartan by oral gavage, efficacy was assessed by echocardiography and cardiac histopathology. Results: TT-00920 had remarkably improved cardiac function, protected against cardiac remodeling and fibrosis in a dose-dependent manner. TT-00920/Valsartan combination showed superior beneficial efficacy when compared to TT-00920 or LCZ696 single agent.Figure 1. TT-00920 improved cardiac function and ventricular remodeling.Figure 2. TT-00920 attenuated cardiac fibrosis in peri-infarct zone. Conclusions: TT-00920 reversed LAD-induced left ventricular dysfunction and remodeling, supporting its potential as a novel therapeutic agent for heart failure. The superior efficacy of TT-00920/Valsartan combination suggests that TT-00920 and renin-angiotensin-aldosterone system inhibitors may have additive therapeutic effects in heart failure.TT-00920 is currently being evaluated in Phase 1 clinical study for safety, tolerability, pharmacokinetics and pharmacodynamics in healthy volunteers (NCT04364789).

scholarly journals Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

2018 ◽  
Vol 45 (5) ◽  
pp. 1797-1806 ◽  
Author(s):  
Anbang Han ◽  
Yingdong Lu ◽  
Qi Zheng ◽  
Jian Zhang ◽  
YiZhou Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathways ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Protective Effects ◽  
Tnf Α ◽  
Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

Blockade of NF-κB improves cardiac function and survival after myocardial infarction

2006 ◽  
Vol 291 (3) ◽  
pp. H1337-H1344 ◽  
Author(s):  
Shunichi Kawano ◽  
Toru Kubota ◽  
Yoshiya Monden ◽  
Takaki Tsutsumi ◽  
Takahiro Inoue ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Diastolic Pressure ◽  
Interstitial Fibrosis ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Targeted Disruption ◽  
Ventricular Rupture ◽  
Inflammatory Processes

NF-κB is a key transcription factor that regulates inflammatory processes. In the present study, we tested the hypothesis that blockade of NF-κB ameliorates cardiac remodeling and failure after myocardial infarction (MI). Knockout mice with targeted disruption of the p50 subunit of NF-κB (KO) were used to block the activation of NF-κB. MI was induced by ligation of the left coronary artery in male KO and age-matched wild-type (WT) mice. NF-κB was activated in noninfarct as well as infarct myocardium in WT + MI mice, while the activity was completely abolished in KO mice. Blockade of NF-κB significantly reduced early ventricular rupture after MI and improved survival by ameliorating congestive heart failure. Echocardiographic and pressure measurements revealed that left ventricular fractional shortening and maximum rate of rise of left ventricular pressure were significantly increased and end-diastolic pressure was significantly decreased in KO + MI mice compared with WT + MI mice. Histological analysis demonstrated significant suppression of myocyte hypertrophy as well as interstitial fibrosis in the noninfarct myocardium of KO + MI mice. Blockade of NF-κB did not ameliorate expression of proinflammatory cytokines in infarct or noninfarct myocardium. In contrast, phosphorylation of c-Jun NH2-terminal kinase was almost completely abolished in KO + MI mice. The present study demonstrates that targeted disruption of the p50 subunit of NF-κB reduces ventricular rupture as well as improves cardiac function and survival after MI. Blockade of NF-κB might be a new therapeutic strategy to attenuate cardiac remodeling and failure after MI.

scholarly journals Qiliqiangxin Capsule Improves Cardiac Function and Attenuates Cardiac Remodeling by Upregulating miR-133a after Myocardial Infarction in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Huiyang Chen ◽  
Lixia Lou ◽  
Dongmei Zhang ◽  
Yizhou Zhao ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Volume Fraction ◽  
Left Ventricular ◽  
Control Group ◽  
Intragastric Administration ◽  
Model Group ◽  
Apoptosis Index ◽  
Cardiac Hemodynamics

Qiliqiangxin capsule (QLC), a natural herb recipe with therapeutic effect from China, has been widely used in clinical practice for attenuating cardiac remodeling induced by myocardial infarction (MI). However, the pharmacological mechanism of QLC on cardiac remodeling after MI is not entirely clear. The present study aims to investigate the effectiveness and mechanisms of QLC on cardiac remodeling induced by MI in rats. The animal model was established by permanently ligating the left anterior descending coronary artery in rats. Subsequently, rats with successful ligation were randomly divided into model group, captopril group, and QLC group. And the control group was operated upon in parallel except ligation, namely, the sham group. All rats were treated through the intragastric administration once a day for 4 weeks. Cardiac hemodynamics was measured after treatment. Then, the left ventricular mass index (LVMI) was examined. The pathological changes were observed by HE staining. The collagen volume fraction (CVF) was detected by Masson trichrome staining. The apoptosis index was obtained by TUNEL fluorescent staining. The miR-133a and mRNA of TGF-β1, CTGF, Caspase9, and Caspase3 were examined by real-time PCR. The protein expressions of TGF-β1, CTGF, Caspase9, Caspase3, and cleaved-Caspase3 were tested by Western blot. Compared with the model group, QLC partially improved cardiac hemodynamics and decreased LVMI. miR-133a was significantly increased in QLC group. In addition, QLC declined CVF by downregulating TGF-β1 rather than CTGF. Meanwhile, QLC decreased the apoptosis index by attenuating Caspase9, Caspase3, and cleaved-Caspase3. This study suggested that QLC could improve cardiac function and partially attenuate cardiac remodeling by attenuating fibrosis and decreasing apoptosis, which might be partially related to miR-133a, TGF-β1, Caspase9, and Caspase3.

scholarly journals Targeted Ablation of Periostin-Expressing Activated Fibroblasts Prevents Adverse Cardiac Remodeling in Mice

2016 ◽  
Vol 118 (12) ◽  
pp. 1906-1917 ◽  
Author(s):  
Harmandeep Kaur ◽  
Mikito Takefuji ◽  
C.Y. Ngai ◽  
Jorge Carvalho ◽  
Julia Bayer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Angiotensin Ii ◽  
Cardiac Function ◽  
Single Cell ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Transcriptional Analysis ◽  
Cardiomyocyte Hypertrophy ◽  
Cardiac Damage

Rationale: Activated cardiac fibroblasts (CF) are crucial players in the cardiac damage response; excess fibrosis, however, may result in myocardial stiffening and heart failure development. Inhibition of activated CF has been suggested as a therapeutic strategy in cardiac disease, but whether this truly improves cardiac function is unclear. Objective: To study the effect of CF ablation on cardiac remodeling. Methods and Results: We characterized subgroups of murine CF by single-cell expression analysis and identified periostin as the marker showing the highest correlation to an activated CF phenotype. We generated bacterial artificial chromosome–transgenic mice allowing tamoxifen-inducible Cre expression in periostin-positive cells as well as their diphtheria toxin-mediated ablation. In the healthy heart, periostin expression was restricted to valvular fibroblasts; ablation of this population did not affect cardiac function. After chronic angiotensin II exposure, ablation of activated CF resulted in significantly reduced cardiac fibrosis and improved cardiac function. After myocardial infarction, ablation of periostin-expressing CF resulted in reduced fibrosis without compromising scar stability, and cardiac function was significantly improved. Single-cell transcriptional analysis revealed reduced CF activation but increased expression of prohypertrophic factors in cardiac macrophages and cardiomyocytes, resulting in localized cardiomyocyte hypertrophy. Conclusions: Modulation of the activated CF population is a promising approach to prevent adverse cardiac remodeling in response to angiotensin II and after myocardial infarction.

scholarly journals Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

2012 ◽  
Vol 302 (10) ◽  
pp. H2112-H2121 ◽  
Author(s):  
Longhu Li ◽  
Husnain Kh. Haider ◽  
Linlin Wang ◽  
Gang Lu ◽  
Muhammad Ashraf
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Short Hairpin Rna ◽  
Pharmacological Intervention ◽  
Hairpin Rna ◽  
Infarction Size ◽  
Lv Remodeling ◽  
Short Hairpin

We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary artery. Immediately after that, an adenoviral vector encoding for shRNA sequence targeting PDE5a (Ad-shPDE5a) was injected intramyocardially, which specifically inhibited PDE5a in the heart. Four weeks later, Ad-shPDE5a treated mice showed significant mitigation of the left ventricle (LV) dilatation and dysfunction as indicated by smaller LV cavity and more preserved ejection fraction and fractional shortening. Infarction size and fibrosis were significantly reduced in Ad-shPDE5a-treated mice. Additionally, more salvaged cardiomyocytes, significantly reduced collagen contents, and higher blood vessel density were observed in Ad-shPDE5a-treated mice. The cytoprotective effects of Ad-shPDE5a were demonstrated in vitro in Ad-shPDE5a transfected cardiomyocytes cultured under oxygen glucose deprivation. Among downstream mediators of PDE5a signaling, cyclic GMP (cGMP) and cGMP-dependent protein kinase G (PKG) were activated with concomitant reduction in caspase-3 activity. However, no significant change in PKA and cAMP activities were observed in Ad-shPDE5a-treated hearts. Inhibition with shRNA improved cardiac remodeling and dysfunction by reducing infarction size and cardiac fibrosis and increased cGMP and PKG activity. These findings suggest that PDE5 inhibition with Ad-shPDE5a is a novel approach for treatment of myocardial infarction.

scholarly journals Salvia miltiorrhizaandCarthamus tinctoriusExtract Prevents Cardiac Fibrosis and Dysfunction after Myocardial Infarction by Epigenetically Inhibiting Smad3 Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jing Yang ◽  
Bo Wang ◽  
Na Li ◽  
Qingqing Zhou ◽  
Wenhui Zhou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Growth Factor ◽  
Cardiac Function ◽  
Myocardial Fibrosis ◽  
Histone Methylation ◽  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Salvia Miltiorrhiza ◽  
Left Ventricular

The incidence of cardiac dysfunction after myocardial infarction (MI) continues to increase despite advances in treatment. Excessive myocardial fibrosis plays a vital role in the development of adverse cardiac remodeling and deterioration of cardiac function. Understanding the molecular and cellular mechanism of the fibrosis process and developing effective therapeutics are of great importance.Salvia miltiorrhizaandCarthamus tinctoriusextract (SCE) is indicated for angina pectoris and other ischemic cardiovascular diseases in China. SCE has been shown to inhibit the platelet activation and aggregation, ameliorate ROS-induced myocardial necrosis by inhibiting mitochondrial permeability transition pore opening, and promote angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF). However, whether SCE has effect on cardiac fibrosis after MI is not fully clear. Here, a mouse model of MI was established to observe the effect of SCE upon survival, cardiac function, myocardial fibrosis, and inflammation. Quantitative PCR and western blot assays were used to determine the expression of genes related to transforming growth factor-β(TGF-β) cascade and inflammatory responsesin vivo. Additionally, the effects of SCE upon the collagen production, TGF-β/Smad3 (SMAD family member 3) signaling, and the levels of histone methylation in primary cardiac fibroblasts were detected. We found that SCE treatment significantly improved survival and left ventricular function in mice after MI. Inhibition of inflammation and fibrosis, as well as decreased expression of Smad3, was observed with SCE treatment. In TGF-β-stimulated cardiac fibroblasts, SCE significantly decreased the expression of collagen,α-smooth muscle actin (α-SMA), and Smad3. Furthermore, SCE treatment downregulated the levels of H3K4 trimethylation (H3K4me3) and H3K36 trimethylation (H3K36me3) at theSmad3promoter region of cardiac fibroblasts, leading to inhibition ofSmad3transcription. Our findings suggested that SCE prevents myocardial fibrosis and adverse remodeling after MI with a novel mechanism of suppressing histone methylation of theSmad3promoter and its transcription.

Testosterone enhances early cardiac remodeling after myocardial infarction, causing rupture and degrading cardiac function

2006 ◽  
Vol 290 (5) ◽  
pp. H2043-H2050 ◽  
Author(s):  
Maria A. Cavasin ◽  
Zhen-Yin Tao ◽  
Ai-Li Yu ◽  
Xiao-Ping Yang
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Neutrophil Infiltration ◽  
Left Ventricular ◽  
Cardiac Rupture ◽  
Myocardial Inflammation ◽  
Histological Changes ◽  
Rupture Rate ◽  
17Β Estradiol ◽  
Infarct Expansion

Cardiac rupture can be fatal after myocardial infarction (MI). Experiments in animals revealed gender differences in rupture rate; however, patient data are controversial. We found a significantly higher rupture rate in testosterone-treated female mice within 1 wk after MI, whereas castration in males significantly reduced rupture. We hypothesized that testosterone may adversely affect remodeling after MI, exaggerating the inflammatory response and increasing cardiac rupture, whereas estrogen may be cardioprotective, attenuating early remodeling and reducing rupture rate. We studied the effect of gender and hormone manipulation on morphological and histological changes during early remodeling after MI in 4-wk-old male and female C57BL/6J mice and how these events could affect cardiac function. Females were randomly divided into 1) sham ovariectomy + placebo (s-ovx + P), 2) s-ovx + testosterone (T), 3) ovx + P, and 4) ovx + T; males were divided into 1) sham castration + P (s-cas + P), 2) s-cas + 17β-estradiol (E), 3) cas + P, and 4) cas + E. At 6 wk after gonadectomy and hormone manipulation, MI was induced. Mice were randomly killed 1, 2, 4, 7, and 14 days after MI. The left ventricle was weighed and sectioned for evaluation of MI size, infarct expansion index (IEI), and neutrophil infiltration. Transthoracic echocardiography was performed in conscious mice in the 14-day group before organ harvest. Cardiac rupture rate and IEI were significantly higher in testosterone-treated females and noncastrated males than in controls; these effects were accompanied by enhanced neutrophil infiltration and pronounced deterioration of cardiac function and left ventricular dilatation. Ovariectomy in females and estrogen supplementation in males did not confer significant protection from cardiac rupture, IEI, or neutrophil infiltration. We concluded that, in mice, high testosterone levels enhance acute myocardial inflammation, adversely affecting myocardial healing and early remodeling, as indicated by increased cardiac rupture, and possibly causing deterioration of cardiac function after MI, and, conversely, estrogen seems to have no significant protective effect in the acute phase after MI.

Abstract 99: Ac-SDKP Protects the Heart From Post-myocardial Infarction Remodeling and Dysfunction in Mice

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Hongmei Peng ◽  
Jiang Xu ◽  
Xiao-Ping Yang ◽  
Xiangguo Dai ◽  
Edward Petersion ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Posterior Wall ◽  
Capillary Density ◽  
Left Ventricular ◽  
Posterior Wall Thickness ◽  
Lv Remodeling ◽  
Anti Inflammatory ◽  
And Function ◽  
Fractional Shortening

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflammatory, anti-fibrotic and pro-angiogenic effects. We previously observed that Ac-SDKP reduces incidence of cardiac rupture in mice with acute myocardial infarction (MI), which is associated with its anti-inflammatory and pro-angiogenic properties. We hypothesized that Ac-SDKP, via its anti-fibrotic and pro-angiogenic actions, ameliorates left ventricular (LV) dilatation and fibrosis, thus improving cardiac function post-MI. C57BL/6J mice were divided into three groups: 1) sham MI, 2) MI + vehicle (VEH), and 3) MI + Ac-SDKP. Ac-SDKP (1.6 mg/kg/day) was given immediately after MI induction ( i.p. via osmotic pump) for 5 weeks. Cardiac remodeling and function were assessed by echocardiography, and interstitial collagen fraction (ICF) and capillary density was determined histologically. We found that Ac-SDKP 1) reduced LV remodeling, evidenced by decreased LV chamber dimensions and areas, and reduced ICF and increased capillary density, with no changes in posterior wall thickness and LV weight (LVW), and 2) improved cardiac function, demonstrated by increased fractional shortening (FS) and ejection fraction (EF) (Table). We conclude that in murine models of MI, Ac-SDKP protects the heart from more severe remodeling and dysfunction, possibly via its anti-fibrotic and pro-angiogenic actions. Thus, the use of Ac-SDKP or its analogues could be a new and effective alternative in restoring cardiac function in patients after MI.

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