Aortic valve calcification is mediated by a differential response of aortic valve interstitial cells to inflammation

Background

Although calcific aortic stenosis is common, calcification of the other three heart valves is not. The aortic valve interstitial cell (VIC) has been implicated in the pathogenesis of aortic stenosis. Proinflammatory stimulation of aortic VICs induces an osteogenic and inflammatory phenotypic change. We hypothesized that the VICs of the other heart valves do not undergo these changes. Using isolated human VICs from normal aortic, mitral, pulmonary, and tricuspid valves, our purpose was to compare the osteogenic response to proinflammatory stimulation via toll-like receptor 4 (TLR-4).

Materials and methods

Aortic, pulmonic, mitral, and tricuspid (n = 4 for each valve type) VICs were isolated from hearts valves explanted from patients undergoing cardiac transplantation. Cells were cultured and grown to confluence in passage 2–6 before treatment with Lipopolysaccharide (LPS) (100–200 ng/mL) for 24 or 48 h. Cells were characterized by immunofluorescent staining. TLR-4 expression was analyzed (immunoblotting, flow cytometry). Bone morphogenetic protein 2 and intercellular adhesion molecule 1 production were determined (immunoblotting). Monocyte chemoattractant protein 1 levels were determined by enzyme-linked immunosorbent assay. Statistics were by Mann–Whitney U test.

Results

TLR-4 stimulation induced bone morphogenetic protein 2 production only in aortic VICs (P < 0.05). Intra-cellular adhesion molecule 1 production and monocyte chemoattractant protein 1 secretion increased in a similar fashion among TLR-4-stimulated VICs from all four valves.

Conclusions

Proinflammatory stimulation induces an osteogenic phenotype in aortic VICs but not mitral, pulmonic, or tricuspid VICs. We conclude that this differential osteogenic response of aortic VICs contributes to the pathogenesis of calcific aortic stenosis.     

Results of surgical treatment of calcified aortic valve stenosis in 80-year-old patients]

The authors discuss surgical treatment of 67 patients for aortic stenosis in 1978-1988. Their ages ranged form 80 to 90 years. In a relatively low operative risk (8.9% mortality) the results provide evidence of marked improvement both in the functional condition (96% of patients are related to the NYHA classes I and II) and in survival (3-year survival 78.2%). The results of balloon valvuloplasty were much poorer. The indications for aortic valvuloplasty are very limited and determined with difficulty.     

Severely calcified bicuspid aortic valve stenosis after valve-sparing root replacement: A word of caution

A 58-year-old man was admitted for reoperation for severe aortic stenosis in a previously preserved bicuspid aortic valve (BAV). He had undergone valve-sparing root replacement (VSSR) for dilated aortic root 6 years ago. Transesophageal echocardiography following VSSR showed good valve function with no aortic incompetence. However, the BAV became stenotic causing shortness of breath. At reoperation, the preserved BAV was noted to be fibrotic and calcified and had a fixed rigid small orifice. It was replaced with a biological valve plus root enlargement. Macroscopic finding showed thickening of the cusps and nodular calcification. Microscopic examination revealed severe nodular calcification.     

A case of aortic bicuspid valve with thrombus formation without severe stenosis and calcification

We encountered a patient with a history of juvenile cerebral infarction with an unknown cause in whom a mass adhering to the aortic valve (AV) surface was observed on echocardiography performed upon the development of heart failure. Mild AV stenosis (AS) with moderate regurgitation was noted, and valve repair was applied. It was found during surgery that the AV was a bicuspid valve (BAV) without calcification, and the mass was an organized thrombus. Thrombus formation on the AV with severe AS in BAV has been reported, but the organic lesion in the AV was mild in this patient.     

Aortic valve replacement in predominant aortic stenosis: What is an appropriate size valve?

Objective This is a retrospective analysis of 94 patients who underwent aortic valve replacement for predominant aortic stenosis between January 1998 and December 2004. Patients and Methods Age ranged from 16 to 70 years (mean 43.2±13.2 years). 73 were male (77.7%). Etiology was rheumatic in 71 (75.5%) and degenerative in 23 (24.5%) patients. On transthoracic echocardiography, the diameter of the aortic annulus ranged from 19 mm to 36mm (mean 28.5±3.0 mm) and the peak systolic gradients ranged from 54 mm to 174 mm of Hg (mean of 109.8±28.8 mmHg). Aortic regurgitation was absent or mild in 76 patients (80.8%) and moderate in rest. A mechanical valve was implanted in 66 patients (70.2%) and a tissue valve in 28 patients (29.8%). Valves of size 23 mm or more were implanted in 75 patients (80%). A valve of 25 mm or larger was implanted in 55 patients (54.3%). Results There were no early deaths. Two patients required permanent pacemaker implantation for complete heart block in the immediate postoperative period. Prosthetic valve thrombosis in one patient was relieved by thrombolysis. Anticoagulant related hemorrhage was seen in two patients. One patient underwent homograft aortic valve replacement for prosthetic valve endocarditis nine months after surgery. Conclusion Isolated aortic valve replacement in patients with predominant aortic stenosis can be performed safely by implanting an adequately large sized prosthesis, without root enlargement in a large majority of patients.     

Balloon valvuloplasty in calcified aortic stenosis: a cause for caution and alarm

Balloon dilation by the percutaneous route has recently been recommended as an alternative to surgical intervention in the management of calcified aortic valvular stenosis. To investigate the validity of balloon valvuloplasty, this procedure was carried out in the operating room under direct vision in 30 patients just prior to excision and replacement of the ossified aortic valve. Changes induced by balloon dilation were evaluated by visual inspection as well as by geometric measurements. By visual observation, balloon valvuloplasty did not have a detectable impact on the valvular anatomy in about 19 of the patients and induced enlargement of the functional aortic orifice judged as "minimal" or "moderate" in only 11. In no patient was there a substantial increase in the functional orifice size. These findings were supported by geometrical measurements. Therefore, we believe that the virtues of this procedure have been grossly overstated by its proponents and that it should be offered only to patients who present a truly forbidding risk by standards of modern surgery.     

The calcified ascending aorta in aortic valve replacement: surgical strategies and results

Purpose

Calcification in the ascending aorta may constitute a major problem during aortic valve replacement (AVR). We examined the distributions of calcification and the associated operative strategies.

Materials and methods

Between 1999 and 2012, 207 consecutive, elderly patients underwent isolated AVR at our center. Computed tomographic scan data were available for all patients, and 105 were found to have at least one segment of calcification. Aortic calcifications were based on the section of the aorta that was calcified: distal, middle, and proximal of the ascending aorta.

Results

Forty-six patients had calcification in the distal zone. In these patients, conventional cannulation was performed in 26 patients, with an associated in-hospital mortality of 7.7 %. Arterial cannulation site was changed from the ascending aorta to somewhere in 20 patients (including other aortic sites in 9 patients, femoral artery in 7 patients, and both femoral and innominate arteries in 4 patients), without any patient deaths. Middle zone calcifications were observed in 70 patients: 63 underwent conventional cross-clamping with particular care (7.9 % mortality), 5 underwent cross-clamping under direct vision during hypothermic circulatory arrest, and 2 underwent balloon occlusion. None of the patients undergoing substitute cross-clamping died. Proximal calcifications were observed in 66 patients; 47 patients underwent conventional transverse aortotomy, with an associated mortality of 8.5 %.

Conclusion

Although the 8.3 % mortality rate in patients undergoing conventional procedures was not negligible, it was lower than the expected 25.9 % estimated by the patient EuroSCOREs. The conventional procedure results are reasonable, but may require a substitute procedure in some cases.     

Increased hsCRP is associated with higher risk of aortic valve replacement in patients with aortic stenosis

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP₀) and after 1 year (hsCRP₁) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9–4.9] to 1.8 [0.8–5.4] mg/l, p?<?0.001) and not receiving AVR (1.90 [0.90–4.10] to 1.3 [0.6–2.9] mg/l, p?<?0.001). In Cox-regression analyses, hsCRP₁ predicted later AVR (HR?=?1.17, p?<?0.001) independently of hsCRP₀ (HR?=?0.96, p?=?0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP₀ and an increase during the first year (AVR_{highCRP0CRP1inc?}=_?47.3% versus AVR_{highCRP0CRP1dec?}=_?27.5%, p?<?0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP₀ eliminating the difference in incidence of AVR between high versus low hsCRP₀ (AVR_{highCRP0CRP1dec?}=_?27.5% versus AVR_{lowCRP0CRP1dec?}=_?25.8%, p?=?0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP₁ or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed.     

Narrowing of the dark valve: aortic stenosis in alkaptonuria

The commonest cardiac pathology in patients with alkaptonuria is aortic stenosis. Patients with alkaptonuria and aortic stenosis may remain asymptomatic until the 6th decade. Surgeons may have to deal with per-operative difficulties as alkaptonuria is a systemic disease. Proper preoperative planning is important. The mechanical valve prosthesis is advisable in a patient with alkaptonuria and aortic stenosis considering disease pathophysiology. We report a 70-year-old male diagnosed with alkaptonuria and aortic stenosis, who underwent aortic valve (mechanical valve prosthesis) and ascending aorta replacement.     

经导管植入国产自膨式主动脉瓣膜治疗老年性主动脉瓣狭窄(附3例报告)

正75岁以上的老年人退行性心脏瓣膜病发病率高达4.6%~([1])。老年性主动脉瓣狭窄(aortic valve stenosis,AS)发病率越来越高。目前外科主动脉瓣膜置换术(surgery aortic valve replacement,SAVR)仍是治疗重度AS的首选方法,但30%~50%的患者因存在严重合并症、无法承受外科手术而出现心力衰竭和心源性猝死。2002年Cribier等~([2])采用经导管主动     

Mechanism of phosphate-induced calcification in rat aortic tissue culture: possible involvement of Pit-1 and apoptosis

Background  

Hyperphosphataemia is a known contributing factor in the progression of vascular calcification in dialysis patients. The cellular mechanisms underlying phosphate-induced calcification are still unclear despite intense study, so in this study, we investigated the possible involvement of the type III sodium-dependent phosphate cotransporter, Pit-1, in an aortic tissue culture model.     

Progression of aortic arch calcification and all-cause and cardiovascular mortality in chronic hemodialysis patients

Objective  

Although aortic arch calcification (AoAC) is reported as a predictor for cardiovascular mortality in the general population, it is unknown whether this is also true in hemodialysis (HD) patients in whom vascular calcification and cardiovascular diseases are highly prevalent.     

Inducible nitric oxide synthase is present in human abdominal aortic aneurysm and promotes oxidative vascular injury

OBJECTIVE: Nitric oxide (NO), catalyzed by inducible NO synthase (iNOS), may be important in the pathophysiologic characteristics of many vascular diseases. Although there is indirect evidence to support the presence of iNOS in abdominal aortic aneurysm (AAA) in human beings, no definitive study has confirm this finding. The present study was designed to assess expression of iNOS in AAA in human beings. Furthermore, the activity of iNOS and the oxidative vascular injury initiated by iNOS were assessed with detection of nitrotyrosine, which is a marker indicative of formation and activity of the NO-derived oxidant peroxynitrite. METHODS: We studied 25 patients with AAA and 10 patients with normal abdominal aortas. In situ hybridization and immunohistochemistry were used in tissue sections to localize iNOS messenger RNA (mRNA) and protein. Double staining with a combination of in situ hybridization and immunohistochemistry was used to simultaneously demonstrate iNOS mRNA expression and its cellular localization. The presence of peroxynitrite was indirectly assessed with immunostaining with anti-nitrotyrosine antibodies. RESULTS: In situ hybridization and immunohistochemistry confirmed the presence of iNOS in media and adventitia of AAA in all 25 patients. Specific cell markers identified iNOS mRNA-positive cells mainly as T and B lymphocytes, macrophages, and smooth muscle cells. Positive immunostaining for nitrotyrosine was present in macrophages and smooth muscle cells. Normal abdominal aorta demonstrated virtually no iNOS or nitrotyrosine expression. CONCLUSION: Stimulated expression of iNOS is associated with degeneration of AAA in human beings, and the activity of this enzyme under such conditions preferentially promotes formation and activity of peroxynitrite and further contributes to oxidative tissue and cellular injury in AAA. This may be important in the pathogenesis of AAA.