Abdominal Aortic Constriction Research Articles

Preventive and Therapeutic Effects of Crocetin in Rats with Heart Failure.

Gardenia is both a food and medicine plant. It is widely used for cardiovascular protection, and its main bioactive ingredient is crocetin. This study aims to observe the therapeutic effects of crocetin on chronic heart failure in rats induced by various etiologies. It further compares the efficacy differences between preventative and treatment administration, varying dosages, and treatment durations, to provide improved guidance for medication in heart failure rats and determine which categories of chronic heart failure rats might benefit most from crocetin. Chronic heart failure models induced by abdominal aorta constriction, renal hypertension, and coronary artery ligation were constructed. By examining cardiac function, blood biochemistry, and histopathology, the study assessed the preventive and therapeutic effects of crocetin on load-induced and myocardial ischemia-induced heart failure. The results showed that in all three models, both treatment and preventative administration of crocetin significantly improved chronic heart failure in rats, especially in preventative administration. The results indicate crocetin may be beneficial for improving symptoms and functional capacity in rats with heart failure. Furthermore, long-term administration was more effective than short-term administration across all three rat models, with therapeutic onset observed over 6 weeks.

Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload.

The impact of myocardial stressors such as high-fat diet (HFD) and pressure overload has been extensively studied. Toll-like receptor 4 (TLR4) deficiency has been suggested to have a protective role in response to these stressors, although some conflicting data exist. Furthermore, there is limited information about the role of TLR4 on cardiac remodeling in response to long-term exposure to stressors. This study aims to investigate the effects of TLR4 deficiency on cardiac histology and physiology in response to chronic stressors. TLR4-deficient (TLR4-/-) and wild-type (WT) mice were subjected to either HFD or a normal diet (ND) for 28 weeks. Another group underwent abdominal aortic constriction (AAC) or a sham procedure and was monitored for 12 weeks. Inflammatory markers, histology, and echocardiography were used to assess the effects of these interventions. TLR4-/- mice exhibited reduced cardiac hypertrophy and fibrosis after long-term HFD exposure compared to ND without affecting cardiac function. On the other hand, TLR4 deficiency worsened cardiac function in response to AAC, leading to decreased ejection fraction (EF%) and increased end-systolic volume (ESV). TLR4 deficiency provided protection against HFD-induced myocardial inflammation but impaired hemodynamic cardiac function under pressure overload conditions. These findings highlight the crucial role of TLR4 and its downstream signaling pathway in maintaining cardiac output during physiologic cardiac hypertrophy in response to pressure overload.

Surgical treatment of thoracoabdominal and abdominal aortic coarctations in adults

Surgical treatment of thoracoabdominal and abdominal aortic coarctations in adults

New insights into the effect of VMP1 on the treatment of pressure overload-induced pathological cardiac hypertrophy: Involving SERCA-regulated autophagic flux

Pathological cardiac hypertrophy is an adaptive reaction in response to pressure or volume overload. Autophagy is critical for damage caused by pathological cardiac hypertrophy. Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane protein that is effective in activating autophagy. However, the role of VMP1 in pathological cardiac hypertrophy and its underlying mechanisms remain elusive. This study was designed to explore the potential mechanisms of VMP1 on pressure overload-induced pathological cardiac hypertrophy. In this work, abdominal aorta constriction (AAC) surgery was used to induce pathological cardiac hypertrophy in male C57BL/6 mice. H9C2 cardiomyocytes were treated with phenylephrine stimulation (PE) to induce the hypertrophic response. The in vivo results revealed that mice with AAC surgery caused pathological cardiac hypertrophy as evidenced by improved cardiac function according to multiple echocardiographic parameters. Moreover, elevated VMP1 expression was also observed in mice after AAC surgery. VMP1 knockdown aggravated changes in cardiac structure, cardiac dysfunction, and fibrosis. Meanwhile, VMP1 knockdown suppressed autophagy and endoplasmic reticulum calcium ATPase (SERCA) activity in heart tissues. H9C2 cardiomyocytes with VMP1 overexpression were used to investigate the specific mechanism of VMP1 in pathological cardiac hypertrophy, and VMP1 overexpression increased autophagic flux by upregulating SERCA activity. In conclusion, these findings revealed that VMP1 protected against pressure overload-induced pathological cardiac hypertrophy by inducing SERCA-regulated autophagic flux. Our results provide valuable insights regarding the pathophysiology of pathological cardiac hypertrophy and clues to a novel target for the treatment of pathological cardiac hypertrophy.

CASE REPORT OF A RARE CAUSE OF SECONDARY HYPERTENSION ILLUSTRATING THE IMPORTANCE OF CARDIO-OBSTETRICS PRECONCEPTION COUNSELING

Objective: Our objective is to illustrate the value of preconception management of rare case of secondary hypertension namely Middle Aortic Coarctation (MAC), which is characterized by a constriction of the upper abdominal aorta. During pregnancy, MAC can lead to feto-maternal unfavorable hemodynamic balance (Fig.1). On the one hand, elevation of the arterial blood pressure (BP) of the upper part of the body increases the maternal cardiovascular risk i.e. stroke or aortic dissection. On the other hand, hypo-perfusion of the lower part of the body reduces uterine perfusion, increases fetal risk of preeclampsia, placental insufficiency or fetal growth restriction. Design and method: Here, we report the case of a 30-year-old woman with severe hypertension and plans to become pregnant. She previously underwent percutaneous transluminal angioplasty (PTA) and aortic stenting and presented with elevated BP in both arms (right 177/117 mmHg, left 180/121 mmHg) and decreased ABI bilaterally (Tab. 1). A computed tomography angiography of the aorta was performed showing an aortic stent in a supraceliac position with 79% in-stent stenosis. She underwent a new PTA with in-stent re-stenting (Fig. 2). Results: Post PCA, the four extremities BP measurements showed a reduction of her BP values and a normalization of the ABI bilaterally (Table 1). 24h-ABPM confirmed the BP reduction (mean 24h- systolic BP of 135 mmHg, diastolic BP of 101 mmHg), but still remaining-elevated. Therefore, we started an antihypertensive treatment with a successful BP control (125/82 mmHg). Conclusions: The management of MAC in already pregnant women can be particularly challenging. Indeed, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are contraindicated. Furthermore, PTA during pregnancy expose the fetus to radiation and reports for CoA angioplasty and stenting during pregnancy are very limited. Herby, we decided on an interventional rather than conservative approach. This case illustrates the importance of preconception screening and treatment of chronic hypertension in women with plans to become pregnant. It highlights the fact that secondary causes of hypertension do not have to be overlooked in this population.

Time of the day negatively impacts immune cell myocardial recruitment and cardiac remodeling induced by abdominal aortic constriction in mice

Consequences of myocardial infarction are more severe when it occurred in the middle of the day (active phase) rather than in the resting phase; and patients operated in the afternoon displayed fewer cardiovascular events after cardiac surgery than patients operated in the morning, suggesting that circadian rhythm may affect cardiovascular events or cardiac remodeling. Interestingly, the immune system plays a critical role in the myocardial remodeling process, and the heart is submitted to circadian variations of immune cells amount. Our objective is to determine the impact of abdominal aortic constriction surgery (AAC) time of day on the severity of cardiac remodeling and the myocardial immune profile induced by the pressure overload in mice. We compared hearts of AAC (ligation 27G) mice operated in their resting phase, at Zeitgeber time 5 (ZT5 n = 6) and early active phase (ZT13 n = 8) with SHAM mice (ZT5 n = 7; ZT13 n = 7). Animal survival, heart weights, and cardiac immunophenotyping analyzed by flow cytometry were studied one week after AAC. Heart weights of AAC mice were increased 7 days after surgery (+20% at ZT5 and +40% at ZT13; P < 0.05 and P < 0.01 compared to SHAM groups respectively). Immune cell analysis showed a 1.7-fold increase in myocardial leukocyte infiltration in ZT13 vs. ZT5 AAC group (P < 0.05) with increased numbers of total, resident, and monocyte-derived macrophages. Myocardial infiltration of dendritic cells and granulocytes was also greater in AAC ZT13 mice compared with AAC ZT5 mice and SHAM groups. Finally, we showed higher mortality in AAC mice operated at ZT13 (vs. ZT5). Time of day when sustained cardiac pressure overload occurs affected cardiac remodeling one week after the onset of AAC; with more pronounced innate immune cells infiltration and hypertrophy of the myocardium at ZT13 (vs. ZT5). Further explorations are needed to determine the link between the increased number of immune cells and the more severe phenotype observed in the ZT13 group.

Iron chelation alleviates multiple pathophysiological pathways in a rat model of cardiac pressure overload.

Iron dysmetabolism affects a great proportion of heart failure patients, while chronic hypertension is one of the most common risk factors for heart failure and death in industrialized countries. Serum data from reduced ejection fraction heart failure patients show a relative or absolute iron deficiency, whereas cellular myocardial analyses field equivocal data. An observed increase in organellar iron deposits was incriminated to cause reactive oxygen species formation, lipid peroxidation, and cell death. Therefore, we studied the effects of iron chelation on a rat model of cardiac hypertrophy. Suprarenal abdominal aortic constriction was achieved surgically, with a period of nine weeks to accommodate the development of chronic pressure overload. Next, deferiprone (100mg/kg/day), a lipid-permeable iron chelator, was administered for two weeks. Pressure overload resulted in increased inflammation, fibrotic remodeling, lipid peroxidation, left ventricular hypertrophy and mitochondrial iron derangements. Deferiprone reduced cardiac inflammation, lipid peroxidation, mitochondrial iron levels, and hypertrophy, without affecting circulating iron levels or ejection fraction. In conclusion, metallic molecules may pose ambivalent effects within the cardiovascular system, with beneficial effects of iron redistribution, chiefly in the mitochondria.

Tropisetron restores normal expression of BAD, SIRT1, SIRT3, and SIRT7 in the rat pressure overload-induced cardiac hypertrophy model.

Tropisetron exerts a protective effect against cardiac complications, particularly cardiac hypertrophy. Oxidative stress and apoptosis are the main contributors to the pathogenesis of cardiac hypertrophy. Sirtuins, a family of histone deacetylases, are connected to cellular oxidative stress signaling and antioxidant defense. Sirtuins are also linked to apoptosis which is an important mechanism in the progression of cardiac hypertrophy to heart failure. Literature also suggests that tropisetron impedes apoptosis, partly mediated through an antioxidant mechanism. Therefore, we examined if tropisetron fights cardiac hypertrophy by adjusting sirtuin family proteins (Sirts) and components of mitochondrial death pathway, Bcl-associated X (BAX), Bcl-2-associated death promoter (BAD). Male Sprague-Dawley rats got divided into four groups, including control (Ctl), tropisetron (Trop), cardiac hypertrophy (Hyp), and hypertrophic rats under tropisetron treatment (Hyp + Trop). Pathological cardiac hypertrophy was induced by surgical abdominal aortic constriction (AAC). The increased expression of brain natriuretic peptide (BNP) in the Hyp group confirms the cardiac hypertrophy establishment. The mRNA levels of SIRT1, SIRT3, SIRT7, and BAD also upregulated in the hypertrophic group (p < 0.001). Postoperational administration of tropisetron for 3 weeks lowered the increased expression of BNP (p < 0.05) and BAD (p < 0.001), though the reduction of BAX expression was statistically insignificant (p > 0.05). Tropisetron treatment also restored the normal level of SIRT1/3/7 genes expression in the Hyp + Trop group (p < 0.05). Present findings suggest that tropisetron can suppress cardiomyocyte hypertrophy progression to heart failure by counteracting BNP, SIRT1, SIRT3, Sirt7, and BAD overexpression-mediated apoptosis in a rat model of cardiac hypertrophy.

Integrated network pharmacology and molecular docking analyses of the mechanisms underlying the antihypertensive effects of lotusine

Hypertension is a modifiable cardiovascular risk factor and cause of death worldwide. Lotusine, an alkaloid extracted from a plant used in traditional Chinese Medicine, has shown anti-hypertensive effects. However, its therapeutic efficacy requires further investigation. We adopted integrated network pharmacology and molecular docking approaches with the aim of investigating lotusine's antihypertensive effects and mechanisms of action in rat models. After identifying the optimal intravenous dosage, we observed the effects of lotusine administration on two-kidney, one-clip (2K1C) rats and spontaneously hypertensive rats (SHRs). Based on network pharmacology and molecular docking analyses, we measured renal sympathetic nerve activity (RSNA) to evaluate lotusine's effect. Finally, an abdominal aortic coarctation (AAC) model was established to evaluate lotusine's long-term effects. The network pharmacology analysis identified 21 intersection targets; of these, 17 were also implicated by the neuroactive live receiver interaction. Further integrated analysis showed high lotusine affinity for the cholinergic receptor nicotinic alpha 2 subunit, adrenoceptor beta 2, and adrenoceptor alpha 1B. Blood pressure of the 2K1C rats and SHRs decreased after treatment with 2.0 and 4.0 mg/kg of lotusine (P < 0.001 versus saline control). We also observed RSNA decreases consistent with the network pharmacology and molecular docking analysis results. Results from the AAC rat model indicated that myocardial hypertrophy was decreased with lotusine administration, demonstrated by echocardiography and hematoxylin and eosin and Masson staining. This study provides insights into the antihypertensive effects and underlying mechanisms of lotusine; lotusine may exert long-term protective effects against myocardial hypertrophy caused by elevated blood pressure.

Protective effect of crocin on chronic heart failure and its mechanism of action

Purpose: To explore the mechanism of action of crocin in rat chronic heart failure (CHF).&#x0D; Methods: One hundred male Sprague Dawley (SD) rats were used to establish CHF rat model by the abdominal aorta constriction method. They were equally randomized into either the model control group (injected with distilled water), crocin low, medium, and high dose groups (daily administered 0.05, 0.1, and 0.75 g/kg of crocin, respectively), or positive control group (daily administration of benazepril hydrochloride), and normal control (without treatment). Parameters evaluated include heart function, inflammatory index changes, and oxidative stress damage.&#x0D; Results: The crocin low, medium, and high dose groups and the positive control group had significantly better cardiac function indices versus the model control group (p &lt; 0.05). High-dose crocin resulted in significantly lower levels of inflammatory factors than a low or medium dose (p &lt; 0.05). Rats that received a medium or high dose of crocin showed significantly increased activity of myocardial antioxidant enzymes, and reduced malondialdehyde (MDA) and reactive oxygen species (ROS) content when compared to those given low doses of crocin (p &lt; 0.05). Protein expressions of Bax-activated caspase-3, and NF-kB decreased significantly with increase in crocin dosage. A high dose of crocin produced a significantly lower apoptotic rate of cardiomyocytes, sodium–calcium exchanger (NCX) level and higher content of sarcoplasmic reticulum calcium pump 2a (SERCA2a) compared with low- and medium-doses.&#x0D; Conclusion: Crocin protects myocardial tissue and enhances ventricular diastolic function of CHF rats through down-regulation of NCX expression and up-regulation of SERCA2a expression. Further studies using clinical CHF models to categorize and analyze crocin-related cellular pathways will be required.

PS-B02-5: NICORANDIL SUPPRESSES ISCHEMIA-INDUCED CARDIAC NOREPINEPHRINE ENHANCEMENT AND VENTRICULAR ARRHYTHMIAS IN PRESSURE OVERLOAD-INDUCED HYPERTROPHIC HEARTS.

Objective: Ventricular arrhythmias are a common cause of sudden death in acute myocardial infarction (MI) and hypertension is a major risk factor of MI. Nicorandil, an ATP sensitive potassium channel (KATP) opener, is usually used in the treatment of acute MI. KATP expresses in nerve terminals as well as cardiomyocytes and KATP in nerve terminals regulates norepinephrine release. The effects of nicorandil on ischemic myocyte are fully defined. On the other hand, the roles of nicorandil on ischemic norepinephrine release in hypertrophic cardiac tissue has remained unexplored. We examined whether nicorandil suppressed interstitial norepinephrine level and ventricular arrhythmia during acute ischemia in chronic pressure overload-induced hypertrophic hearts. Design and Methods: Rats were divided into two groups: abdominal aortic constriction (AAC) group and sham-operated (Sham) group. Four weeks after constriction, cardiac geometry and function were examined using echocardiography and hemodynamic measurements, and cardiac tissues were stained with hematoxylin and eosin and Sirius Red for histological examinations. In other rats, 4 weeks after constriction myocardial ischemia was induced by the left anterior descending artery occlusion for 100 minutes in the presence or absence of intravenous infusion of nicorandil. Cardiac interstitial norepinephrine concentration in ischemic region was measured using the microdialysis method. Ventricular arrhythmias were monitered by ECG during whole ischemic period. Results: Four weeks after constriction, remarkable left ventricular wall thickening and diastolic dysfunction were observed in AAC group. In histological examination, remarkable myocyte hypertrophy and interstitial fibrosis were observed in AAC group. Before ischemia, ventricular arrhythmia was not found in both groups. Number of ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, was increased in early ischemic period (−20 min) in both groups, and was grater in AAC group. Before ischemia, interstitial norepinephrine concentration in cardiac tissue was higher level in AAC group than in Sham group, and ischemia increased norepinephrine concentration in both groups. Nicorandil administration in ischemic period significantly suppressed the number of ventricular arrhythmias and abolished the ventricular tachycardia and fibrillation without hemodynamic alterations in hypertrophic hearts. Nicorandil also attenuated epinephrine enhancement in acute ischemic period in hypertrophic hearts. Conclusion: Ischemia-induced ventricular arrhythmias were more frequent and severe in hypertrophic hearts and associated with high interstitial norepinephrine concentration. Nicorandil suppressed ischemia-induced interstitial norepinephrine release by neuronal KATP opening, which attenuated ventricular arrhythmias in pressure overload-induced hypertrophic hearts.

Cardiac remodeling induced by early postnatal abdominal aorta constriction in rats: Sex differences in heart function and geometry

Cardiac remodeling induced by early postnatal abdominal aorta constriction in rats: Sex differences in heart function and geometry

Abstract 14533: Molecular Imaging of Fibroblast Activity in Pressure Overload Heart Failure

Introduction: Cardiac fibrosis, mediated by the activation of cardiac fibroblasts, is critical in pressure overload-induced heart failure. Fibroblast activation protein (FAP), specifically expressed by activated fibroblasts, can be visualized by radiolabeled FAP inhibitors (FAPI) PET/CT. Hypothesis: To evaluate whether 68Ga-FAPI-04 could characterize the early stages of cardiac fibrosis in pressure overload heart failure. Methods: Sprague-Dawley rats underwent abdominal aortic constriction (AAC) (n = 12) and sham surgery (n = 10). All rats were scanned with 68 Ga-FAPI-04 PET/CT at 2, 4, and 8 weeks after surgery. Cardiac function was measured by echocardiography. The expression of FAP in the myocardium was detected by immunohistochemistry. Results: Compared with the sham group, the AAC group presented with decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in diastole (LVIDd) and systole (LVIDs) at 4 and 8 weeks (all p &lt; 0.01). The AAC group showed higher 68 Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8 weeks, respectively (all p &lt; 0.001), and FAPI increased significantly from 2 to 8 weeks. Immunohistochemistry confirmed the higher density of the FAP + area in the AAC group. The intensity of the 68 Ga-FAPI-04 PET signal correlated with the density of the FAP + area on histology (p &lt; 0.001). The expression of the 68 Ga-FAPI-04 at 4 weeks correlated with the deterioration of cardiac function at 8 weeks (EF: R = -0.87; FS: R = -0.72; LVIDd: R = 0.77; LVIDs: R= 0.79; all p &lt; 0.001). The AAC group also showed an increased 68 Ga-FAPI-04 signal in the liver, peaking at 4 weeks and then declining. Cardiac and liver PET signals directly correlated at 4 weeks in the AAC group (R = 0.69, p = 0.0010). A combination of the FAPI intensity in the heart and liver at 4 weeks better predicted the deterioration of cardiac function at 8 weeks. Conclusion: The activated fibroblasts in the heart and liver after pressure overload can be monitored by 68 Ga-FAPI-04 PET/CT. This imaging technique reveals an early fibrotic link in cardio-liver interactions and could better predict nonischemic heart failure prognosis.

A Heart Failure Model Established by Pressure Overload Caused by Abdominal Aortic Contraction in Rat.

Heart failure is a complex clinical syndrome in which ventricular filling or ejection capacity is impaired due to structural or functional diseases of the heart. In order to establish a stable heart failure model, we investigated cardiac parameters in rats with abdominal aortic contraction and normal rats, including the left ventricular posterior wall diameter (LVPWd), the interventricular septum thickness of end-diastolic (IVSd), the left ventricular end-diastolic diameter (LVEDd), the left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS). Rats were randomly divided into experimental group (n = 20) and control group (n = 20). The experimental group underwent modified abdominal aortic constriction, while the control group only isolated the abdominal aorta without constriction. The results showed that the survival rate of rats in the experimental group was 85% after one week of operation, while the survival rate of rats in the control group was 100%. Five weeks after operation, the left ventricular posterior wall diameter (LVPWd) and the interventricular septum thickness of end-diastolic (IVSd) in the experimental group were all increased compared with those in the control group, and the differences were statistically significant (p < 0.05); the left ventricular end-diastolic diameter (LVEDd) in the experimental group showed an increasing trend compared with the control group, but p > 0.05; compared with the control group, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the experimental group showed downward trend, but p > 0.05. 10 weeks after operation, the LVPWd, IVSd, and LVEDd of the experimental group were increased compared with the control group, p < 0.05, and the LVEF and LVFS of the experimental group were decreased compared with the control group, p < 0.05. Compared with the control group, the BNP of the experimental group increased significantly, p < 0.05. The heart weight index and left ventricular weight index of rats in the experimental group were significantly higher than those in the control group, p < 0.05. HE staining showed that the myocardial cells in the experimental group increased in volume, disordered cell arrangement, widened gaps, increased nuclear hyperchromia, and uneven staining. This paper provides a theoretical basis for the study of heart failure.

Mechanical stretch aggravates vascular smooth muscle cell apoptosis and vascular remodeling by downregulating EZH2

Enhancer of zeste homolog 2 (EZH2) was recently found to play an important role in cardiovascular disease. However, the role of EZH2 in vascular remodeling induced by mechanical stretch is poorly understood. The aim of the present work was to investigate the role of EZH2 in regulating smooth muscle cell function through mechanical stretch assays and to explore the underlying mechanisms. WT C57BL/6J mice underwent sham surgery or abdominal aortic constriction. The level of EZH2 expression was determined by Western blotting and immunohistochemical staining. We demonstrated the thickness of vascular remodeling by HE staining. JASPAR was used to predict transcription factors that could affect EZH2. Chromatin immunoprecipitation was used to substantiate the DNAprotein interactions. Promoter luciferase assays were performed to demonstrate the activity of the transcription factors. We found that in vivo, AAC significantly reduced EZH2 protein levels in the thoracic aorta. Smooth muscle-specific overexpression of EZH2 was sufficient to attenuate the AAC-induced reduction in trimethylation of Lys-27 in histone 3 and thickening of the arterial media. Administration of GSK-J4 (an inhibitor of H3K27me3 demethylase) induced the same effects. In addition, we found that mechanical stretch regulated the expression of EZH2 through the Yes-associated protein (YAP)- transcriptional factor TEA domain 1 (TEAD) pathway. TEAD1 bound directly to the promoter of EZH2, and blocking the YAP-TEAD1 interaction inhibited EZH2 downregulation due to mechanical stretch. This study reveals that mechanical stretch downregulates EZH2 through the YAP-TEAD1 pathway, thereby aggravating smooth muscle cell apoptosis and vascular remodeling.

Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction induced by abdominal aorta constriction through cyclic guanosine monophosphate-dependent protein kinase Signaling Pathway.

To determine whether Shunxin decoction improves diastolic function in rats with heart failure with preserved ejection fraction (HFpEF) by regulating the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. Except for control group 8 and sham surgery group 8, the remaining 32 male Sprague-Dawlay rats were developed into HFpEF rat models using the abdominal aorta constriction method. These rats in the HFpEF model were randomly divided into the model group, the Shunxin high-dose group, the Shunxin low-dose group, and the Qiliqiangxin capsule group. The three groups received high-dose Shunxin decoction, low-dose Shunxin decoction, and Qiliqiangxin capsule by gavage, respectively, for 14 d. After the intervention, the diastolic function of each rat was evaluated by testing E/A, heart index, hematoxylin-eosin staining, Masson, myocardial ultrastructure, and N-terminal pro-brain natriuretic peptide (NT-proBNP). The Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) software was used to predict targets for which Shunxin decoction acts on the cGMP-PKG pathway. Natriuretic peptide receptor A (NPRA) and guanylate cyclase (GC) were detected by immunohistochemistry, and eNOS, phosphodiesterase 5A (PDE5A), and cGMP-dependent protein kinase 1(PKG I) were determined by Western blotting. Compared to the model group, the thickness of the interventricular septum at the end of diastole (IVSd) and the thickness of the posterior wall at the end of diastole (PWd) of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group were all significantly reduced ( < 0.01). Furthermore, Shunxin decoction high-dose group E/A value was decreased ( < 0.01). Compared to the model group, the expression of NPRA and GC increased in the Shunxin decoction low-dose group and the Qiliqiangxin capsule group ( < 0.01). Compared to the model group, the expressions of eNOS and PKG I increased ( < 0.05) in the Shunxin decoction high-dose group. The expression of PDE5A expression decreased in the myocardium of the Shunxin decoction high-dose group, Shunxin decoction low-dose group, and Qiliqiangxin capsule group compared to the model group ( < 0.01). Shunxin decoction can improve diastolic function in rats with HFpEF. It increases the expression of NPRA, GC, and eNOS in the myocardial cell cGMP-PKG signaling pathway, upregulates cGMP expression, decreases PDE5A expression to reduce the cGMP degradation. Thus, the cGMP continually stimulates PKG I, reversing myocardial hypertrophy and improving myocardial compliance in HFpEF rats.

Molecular imaging of fibroblast activity in pressure overload heart failure using [68Ga]Ga-FAPI-04 PET/CT.

We aimed to evaluate whether [68Ga]Ga-FAPI-04 PET/CT could characterize the early stages of cardiac fibrosis in pressure overload heart failure. Sprague-Dawley rats underwent abdominal aortic constriction (AAC) (n = 12) and sham surgery (n = 10). All rats were scanned with [68Ga]Ga-FAPI-04 PET/CT at 2, 4, and 8weeks after surgery. The expression of fibroblast activation protein (FAP) in the myocardium was detected by immunohistochemistry. [68Ga]Ga-FAPI-04 PET signal and FAP expression were compared between two groups. Compared with the sham group, the AAC group presented with decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in diastole (LVIDd) and systole (LVIDs) at 4 and 8weeks (all p < 0.01). The AAC group showed higher [68Ga]Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8weeks, and FAPI increased significantly from 2 to 8weeks (all p < 0.001). Immunohistochemistry confirmed the higher density of the FAP+ area in the AAC group. The intensity of the [68Ga]Ga-FAPI-04 correlated with the density of the FAP+ area (p < 0.001). The expression of the [68Ga]Ga-FAPI-04 at 4weeks correlated with the deterioration of cardiac function at 8weeks (EF: R = - 0.87; FS: R = - 0.72; LVIDd: R = 0.77; LVIDs: R = 0.79; all p < 0.001). The AAC group also showed an increased [68Ga]Ga-FAPI-04 signal in the liver, peaking at 4weeks and then declining. Cardiac and liver PET signals correlated at 4weeks in the AAC group (R = 0.69, p = 0.0010), suggesting an early fibrotic link between organs. A combination of the [68Ga]Ga-FAPI-04 intensity in the heart and liver at 4weeks better predicted the deterioration of cardiac function at 8weeks. The activated fibroblasts in the heart and liver after pressure overload can be monitored by [68Ga]Ga-FAPI-04 PET/CT, which reveals an early fibrotic link in cardio-liver interactions and could better predict nonischemic heart failure prognosis.

MiR-212 Promotes Cardiomyocyte Hypertrophy through Regulating Transcription Factor 7 Like 2.

To explore the role and possible mechanism of miRNA-212 in heart failure (HF). The rat model of abdominal aortic constriction was constructed, the changes of myocardial morphology were observed by hematoxylin-eosin (HE) staining, and the hypertrophy-related marker molecules were detected by quantitative real-time polymerase chain reaction (qRT-PCR). At the cellular level, phenylephrine and angiotensin II were added to induce cardiomyocyte hypertrophy. The overexpression of miR-212 adenovirus was constructed, and the expression of miR-212 was overexpressed, and its effect on cardiac hypertrophy (CH) was detected by immunofluorescence and qRT-PCR. Then, the mechanism of miR-212 regulating CH was verified by website prediction, luciferase reporter gene assay, qRT-PCR, and western blotting assay. In the successfully constructed rat model of abdominal aortic constriction and cardiomyocyte hypertrophy, ANP and myh7 were dramatically increased, myh6 expression was decreased, and miRNA-212 expression was increased. Overexpression of miRNA-212 in cardiomyocytes can promote cardiomyocyte hypertrophy, while knocking down miR-212 in cardiomyocytes can partially reverse cell hypertrophy. In addition, miR-212 targets TCF7L2 and inhibits the expression of this gene. miRNA-212 targets TCF7L2 and inhibits the expression of this gene, possibly through this pathway to promote cardiomyocyte hypertrophy.

Histologic and morphologic character of pediatric abdominal aortic developmental coarctation and hypoplasia: Presented at the Forty-fifth Annual Meeting of the Midwestern Vascular Surgical Society, Chicago, Illinois, September 9, 2021.

Histologic and morphologic character of pediatric abdominal aortic developmental coarctation and hypoplasia: Presented at the Forty-fifth Annual Meeting of the Midwestern Vascular Surgical Society, Chicago, Illinois, September 9, 2021.

Nicorandil Suppresses Ischemia-Induced Norepinephrine Release and Ventricular Arrhythmias in Hypertrophic Hearts.

Ventricular arrhythmias (VAs) are a common cause of sudden death in acute myocardial infarction (MI), for which hypertension is a major risk factor. Nicorandil opens ATP-sensitive potassium (KATP) channels, which are expressed by nerve terminals and cardiomyocytes and regulate the release of norepinephrine (NE). However, the effects of nicorandil on ischemic NE release in cardiac tissue remain unclear. Therefore, we herein investigated whether nicorandil suppressed interstitial NE concentrations and VAs during acute MI in pressure overload-induced hypertrophic hearts. Rats were divided into two groups: an abdominal aortic constriction (AAC) group and sham-operated (Sham) group. Four weeks after constriction, cardiac geometry and functions were examined using echocardiography and hemodynamic analyses. Myocardial ischemia was induced by coronary artery occlusion for 100min with or without the administration of nicorandil. VAs were assessed by electrocardiography, and NE concentrations in the ischemic region were measured using a micro-dialysis method. AAC induced left ventricular hypertrophy with diastolic dysfunction. VAs markedly increased in the early phase (0-20min) of ischemia in both groups and were more frequent in the AAC group. Cardiac interstitial NE concentrations were higher in the AAC group before ischemia and significantly increased during ischemia in both groups. Nicorandil significantly suppressed ischemia-induced VAs and NE increases in the AAC group. Ischemia-induced VAs were more frequent in hypertrophic hearts and associated with high interstitial concentrations of NE. The attenuation of ischemia-induced increases in NE through neuronal KATP opening by nicorandil may suppress ischemia-induced VAs in hypertrophic hearts.