Role of STIM1 in the Regulation of Cardiac Energy Substrate Preference.

The heart requires a variety of energy substrates to maintain proper contractile function. Glucose and long-chain fatty acids (FA) are the major cardiac metabolic substrates under physiological conditions. Upon stress, a shift of cardiac substrate preference toward either glucose or FA is associated with cardiac diseases. For example, in pressure-overloaded hypertrophic hearts, there is a long-lasting substrate shift toward glucose, while in hearts with diabetic cardiomyopathy, the fuel is switched toward FA. Stromal interaction molecule 1 (STIM1), a well-established calcium (Ca2+) sensor of endoplasmic reticulum (ER) Ca2+ store, is increasingly recognized as a critical player in mediating both cardiac hypertrophy and diabetic cardiomyopathy. However, the cause-effect relationship between STIM1 and glucose/FA metabolism and the possible mechanisms by which STIM1 is involved in these cardiac metabolic diseases are poorly understood. In this review, we first discussed STIM1-dependent signaling in cardiomyocytes and metabolic changes in cardiac hypertrophy and diabetic cardiomyopathy. Second, we provided examples of the involvement of STIM1 in energy metabolism to discuss the emerging role of STIM1 in the regulation of energy substrate preference in metabolic cardiac diseases and speculated the corresponding underlying molecular mechanisms of the crosstalk between STIM1 and cardiac energy substrate preference. Finally, we briefly discussed and presented future perspectives on the possibility of targeting STIM1 to rescue cardiac metabolic diseases. Taken together, STIM1 emerges as a key player in regulating cardiac energy substrate preference, and revealing the underlying molecular mechanisms by which STIM1 mediates cardiac energy metabolism could be helpful to find novel targets to prevent or treat cardiac metabolic diseases.

[Surgery therapy of Crohn disease complicated with fistula].

OBJECTIVE: To investigate the surgical treatment of Crohn disease(CD) complicated with perforation or fistula. METHODS: The clinical data of 24 CD cases complicated with perforation or fistula treated in our department from Jan. 1980 to Apr. 2005 were analyzed retrospectively. RESULTS: There were 24 cases of CD complicated with perforation or fistula among 181 CD patients,and the incidence of perforation or fistula was 13.3%. Steroid treatment before perforation was given in 8 patients, while not in 9 patients and unclear in 7 patients. Eighteen patients had single perforation, 4 patients two free perforations and 2 patients more than three extra-abdominal fistula. Emergency operation was performed in 8 cases and selective operation in 16 cases. Five cases had postoperative complications including incision infection in 2, intra-abdominal abscess in 2 and stomal fistula in one case, and were all cured by surgical drainage and anti-infection treatment. The morbidity rate was 20.8%. The postoperative mortality rate was 12.5% (3/24). Eighteen patients were followed up from 6 months to 18 years, and the 5-year recurrent rate was 16.7%. The 10-year reoperation rate was 33.3%. CONCLUSIONS: Steroid use is not the main cause of perforation or fistula in CD. Perforation or fistula is the definite indication for surgical treatment.