Fuhua Huang

The stented elephant trunk procedure combined total arch replacement for Debakey I aortic dissection: operative result and follow-up

The stented elephant trunk technique in aortic arch replacement combined with transaortic stented graft implantation into the descending aorta has been introduced as a means of eliminating the residual false lumen in the descending thoracic aorta and improving long-term outcomes of surgical intervention for Debakey I aortic dissection. This report summarizes the operative and follow-up data with this new procedure. Between August 2004 and May 2009, 28 stented elephant trunk operations were performed for Debakey I aortic dissection at Nanjing First Hospital. A 10 cm long woven Dacron graft was implanted through the aortic arch during hypothermic circulatory arrest. Patent false lumina were evaluated using computed tomography three months after the operation. Mean cardiopulmonary bypass time was 213.2±47.2 min, and selected cerebral perfusion time was 38.8±9.7 min. Hospital mortality was 14.3% (4/28). Thrombus obliteration of the residual false lumen in the descending aorta was observed in 91.7% of the aortic dissections three months postoperatively. The survival rate was 87.5% at five years and the freedom from reoperation rate was 91.7%. Total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta is an effective treatment for Debakey type I aortic dissection.

Caspase Recruitment Domain 6 Protects Against Cardiac Hypertrophy in Response to Pressure Overload

Caspase recruitment domain 6 (CARD6), a crucial member of the CARD family, was initially shown to be involved in the immune system and oncogenesis. However, the role of CARD6 in chronic pressure overload–induced cardiac hypertrophy remains unexplored. To evaluate the impact of CARD6 on pathological cardiac hypertrophy, cardiac-specific CARD6 knockout mice and transgenic mice with cardiac-specific CARD6 overexpression were generated and subjected to aortic banding for 4 weeks. Our results demonstrated that CARD6-deficient mice aggravated aortic banding–triggered cardiac hypertrophy, ventricular dilation, fibrosis, and dysfunction, as measured by echocardiography, immunostaining, and molecular/biochemical analyses. Conversely, CARD6-overexpressing mice exhibited an attenuated hypertrophic response to chronic pressure overload. Similarly, using cultured neonatal rat cardiomyocytes, we found that adenovirus vector–driven overexpression of CARD6 dramatically limited angiotensin II–induced myocyte hypertrophy, whereas knockdown of CARD6 by AdshCARD6 (adenoviral short hairpin CARD6) exhibited the opposite phenotypes. Furthermore, analysis of the signaling events in vitro and in vivo revealed that CARD6-mediated protection against cardiac hypertrophy was attributed to the interruption of mitogen-activated protein kinase kinase (MEK) kinase-1–dependent MEK-extracellular signal-regulated protein kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) activation. Altogether, these data indicated that CARD6 serves as a novel cardioprotective factor via negative regulation of MEK kinase-1–dependent MEK-ERK1/2 and JNK1/2 signaling. Thus, our study suggests that CARD6 may be a novel target for the treatment of pathological cardiac hypertrophy and failure.

Proteomic analysis of myocardial tissue from the border zone during early stage post-infarct remodelling in rats

Long‐term outcome of patients after myocardial infarction (MI) largely depends on the extent of post‐infarct remodelling. To explore the molecular mechanism of remodelling, comparative proteomic analysis was undertaken to identify differential myocardial proteome profiles expressed in the border zone of the post‐MI heart.

Proteomics analysis of human pericardial fluid

Pericardial fluid (PF) is considered as a biochemical window of heart. To date, there have been limited attempts to perform an in‐depth analysis of the PF proteome. In this study, an SDS‐PAGE‐LC‐MS/MS platform was utilized to explore depleted PF, which showed great coverage of low‐abundant proteins. In total, 1007 nonredundant proteins were identified with at least two peptides. This is the first comprehensive analysis of human PF proteome and provides a foundation for further application of PF in cardiovascular research. The data have been deposited to the ProteomeXchange with identifier PXD000194.

Comparison of off-pump and on-pump coronary endarterectomy for patients with diffusely diseased coronary arteries: early and midterm outcome

BackgroundCoronary endarterectomy (CE) is an alternative for the diffusely diseased left anterior descending (LAD), but its mid and long term results are largely questionable. This study is to compare the early to mid-term results between off-pump and on-pump coronary endarterectomy with coronary artery bypass grafting.Methods212 consecutive patients underwent CE and bypass grafting for diffusely diseased LAD. Ninety-two patients undergoing CE with off-pump (group off-pump) were compared with 120 patients undergoing CE with on-pump (group on-pump). The main preference for selection to an off-pump CE surgery were the preoperative high risk factors, especially previous cerebrovascular accident、chronic obstructive pulmonary disease (COPD)、calcified ascending aorta and right coronary artery (RCA) critical stenosis >90%.ResultsThere were three deaths in this group with total operative mortality of 1.4%. The perioperative mortality of group off-pump (1.1%) was similar with that of group on-pump (1.7%). The postoperative myocardial infarctions rate was 2.8%. There was no significant difference as for the morbidity between the group off-pump and group on-pump. Among survivors, the patency rate of the LIMA–LAD anastomosis was 89.4%. There was no difference as for the grafts patency rate between the two groups. Kaplan–Meier survival revealed no significant difference between the two groups. Kaplan-Meier freedom from cardiac events requiring hospital re-admission and angina recurrence were similar in both groups.ConclusionsOn-pump or off-pump CE is a good technique with the same early and mid-term outcomes. In the series of off-pump CE, we have shown that the effect of OPCABG with CE appears to be durable, and mid-term clinical outcomes are encouraging. Despite the higher risk profile, hospital mortality and major complications in our study are comparable to those for CCE.

Comparative study on the histomorphology and molecular biology of radial artery conduits in patients with diabetes mellitus who underwent coronary bypass surgery.

We studied the impact of diabetes mellitus (DM) on the radial artery (RA) in 30 patients with DM and 30 non-diabetic patients undergoing coronary artery bypass grafting with autologous RA. RAs were recorded as normal if there was no cellular or stromal tissue between the endothelium and the internal elastic lamina. The RA was normal in 26.7% of diabetic and 76.7% of non-diabetic patients (p = 0.000298). Intimal thickness index and intima:media ratio were higher in the former than in the latter (p < 0.05; p < 0.05), with no significant difference in luminal narrowing (p > 0.05). Electron microscopy scores were lower in the non-diabetic group (p < 0.001); endothelial nitric oxide synthase (eNOS) protein expression and optical density were higher (p < 0.001). Von Willebrand factor and endothelin-1 messenger RNA (mRNA) levels were higher in the DM patients (p < 0.001). The quality of the RA in patients with DM was thus inferior to that in non-diabetic patients. Care should be taken when selecting RA as a conduit in patients with DM.

Critical Role of ADAMTS2 (A Disintegrin and Metalloproteinase With Thrombospondin Motifs 2) in Cardiac Hypertrophy Induced by Pressure OverloadNovelty and Significance

ADAMTS2 (A Disintegrin and Metalloproteinase With Thrombospondin Motifs 2) is recognized as a metalloproteinase that promotes the cleavage of amino propeptides of types I, II, III, and V procollagens. However, the role of ADAMTS2 in the heart has not yet been defined. Herein, we observed the upregulated expression of ADAMTS2 in failing human hearts and hypertrophic murine hearts. Mice lacking ADAMTS2 display exacerbated cardiac hypertrophy on pressure overload–induced hypertrophic response, whereas mice with cardiac-specific overexpression of ADAMTS2 display alleviation of this detrimental phenotype. Consistent with these results, in vitro loss or gain of function experiments in neonatal rat cardiomyocytes confirmed that ADAMTS2 negatively regulates cardiomyocyte hypertrophy in response to Ang II. Mechanistically, blockage of the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)–dependent signaling pathway with specific inhibitors both in vivo and in vitro could rescue the aggravated hypertrophic response to the loss of ADAMTS2. Collectively, we propose that ADAMTS2 regulates the hypertrophic response through inhibiting the activation of the PI3K/AKT-dependent signaling pathway. Because ADAMTS2 is an extracellular protein, it could be effectively manipulated using pharmacological means to modulate cardiac hypertrophy.

Partial aortic root remodeling for root reconstruction in patients with acute type A dissection

Abstract In the present study, we reported our experience with partial aortic root remodeling for root reconstruction in patients with acute type A dissection, which involves in non-coronary sinus and/or the right coronary sinus with just one trimmed Dacron graft. Between February 2001 and May 2010, we performed partial aortic root remodeling in 40 patients, who underwent emergency surgical intervention. The dissected sinuses were excised leaving a 3-5 mm rim of the aortic wall from the attached aortic valve cusps. A short piece (4-5 cm) of collagen coated woven polyester vascular prosthesis was trimmed with one or two “tongues” to reconstruct the non-coronary sinus and/or the right coronary sinus, but without using separated patches. Additional procedures were including hemi-arch replacement in 11 patients, and total arch replacement plus stent-elephant trunk in 20 patients. The mean follow-up time was 36.4±3.6 months. In-hospital mortality was only 5.0% (2/40); furthermore, 3 (8.6%) patients underwent re-operation of the aortic valve and 2 (5.7%) patients died during follow-up. At the end of follow-up, trivial or no aortic regurgitation was found in 33 patients, but mild aortic regurgitation was found in 2 patients. Our data suggest that the early and mid-term results of partial aortic root remodeling were favorable, and it restored valve durability and function. Thus, the use of technique for root reconstruction in patients with acute type A dissection should be vigorously encouraged.

Regulatory role of IKKɑ in myocardial ischemia/reperfusion injury by the determination of M1 versus M2 polarization of macrophages

The IκB kinase (IKK) complex plays a well-documented role in cancer and immune system. This function has been widely attributed to its role as the master regulator of the NF-κB family. Particularly, IKKɑ, a member of IKK complex, is reported to have various regulating effects in inflammatory and malignant diseases. However, its role as well as its mechanism of function in macrophages following myocardial ischemia and reperfusion (I/R) injury remains unexplored. In vivo, sham or I/R operations were performed on macrophage-specific IKKɑ knockout (mIKKɑ-/-) mice and their IKKɑflox/flox littermates. We ligated the left anterior descending (LAD) coronary artery of I/R groups simulating ischemia for 30 min, followed by a reperfusion period of 3 days and 7 days, respectively. The hearts of mIKKɑ-/- mice exhibited significantly increased inflammation and macrophage aggregation as compared to their IKKɑflox/flox littermates. Moreover, in the mIKKɑ-/- group subjected to I/R macrophages had a tendency to polarize to M1 phenotype. In vitro, we stimulated RAW264.7 cells with Lipopolysaccharides (LPS) after infection by the lentivirus, either knocking-down or overexpressing IKKɑ. We discovered that a deficiency of IKKɑ in RAW264.7 caused increased expression of pro-inflammatory markers compared to normal RAW264.7 after LPS stimulation. Inversely, pro-inflammatory factors were inhibited with IKKɑ overexpression. Mechanistically, IKKɑ directly combined with RelB to regulate macrophage polarization. Furthermore, IKKɑ regulated MEK1/2-ERK1/2 and downstream p65 signaling cascades after LPS stimulation. Overall, our data reveals that IKKɑ is a novel mediator protecting against the development of myocardial I/R injury via negative regulation of macrophage polarization to M1 phenotype. Thus, IKKɑ may serve as a valuable therapeutic target for the treatment of myocardial I/R injury.

Cortistatin attenuates angiotensin II-induced abdominal aortic aneurysm through inactivation of the ERK1/2 signaling pathways

Abdominal aortic aneurysm (AAA) is a fatal disease that is associated with chronic inflammation in the vessel wall. Cortistatin is implicated in inflammation, vascular smooth muscle cell migration and other cardiovascular pathologies. But, the hypothetical effect of cortistatin on AAA remains uncertain. We investigated the effect of cortistatin administration to angiotensin (Ang) II-induced AAA formation in apolipoprotein E deficient (Apoe-/-) mice. We showed that cortistatin administration significantly suppresses incidence and severity of AAA in Apoe-/- mice. A significant increase in macrophage infiltration, excretion of inflammatory cytokines, activities and expression levels of MMP2 and MMP9, reactive oxygen species levels and cell apoptosis in aneurysmal aortic wall of Apoe-/- mice infused with Ang-II, and these events were significantly alleviated by co-treatment with cortistatin. Mechanistic studies showed that the protective effects of cortistatin were related to the blocking of ERK1/2 signaling pathways, while does not was not actually affect JNK, P38 phosphorylation. In conclusion, cortistatin appears to play an essential role in the formation of AAA and indicate cortistatin may as novel therapeutic option for AAA.