[Effects of matrix metalloproteinase-9 and tissue inhibitor-1 of metalloproteinase expression on atrial structural remodeling during chronic atrial fibrillation].

OBJECTIVE: To investigate the matrix metalloproteinase-9 (MMP-9) and tissue inhibitor-1 of metalloproteinase (TIMP-1) mRNA and protein expression in chronic fibrillating human atria and to evaluate the influence of MMP-9 and TIMP-1 expression on the progress of atrial structural remodeling. METHODS: Twenty-four patients with chronic atrial fibrillation (AF) and 12 patients with sinus rhythm as control group underwent transthoracic echocardiography and left atrial appendage (LAA) tissue samples were obtained from these patients during mitral/aortic valve replacement operation. MMP-9 and TIMP-1 protein expressions were detected by immunohistochemistry and their mRNA expressions were determined by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The left atrial and right atrial diameters increased significantly in the fibrillation group in comparison with the control group (57 +/- 6 vs 45 +/- 7, 62 +/- 10 vs 51 +/- 17, P < 0.05 approximately 0.001) The expressions of MMP-9 mRNA and protein in the LAA tissue of the AF group is upregulated (0.70 +/- 0.12 vs 0.53 +/- 0.22, and 2.25 +/- 0.73 vs 1.12 +/- 0.58, P < 0.05 approximately 0.001) and the expressions of TIMP-1 mRNA and protein were downregulated significantly (0.20 +/- 0.07 vs 0.31 +/- 0.15, and 1.12 +/- 0.48 vs 1.75 +/- 0.46, P < 0.05 approximately 0.01). The MMP-9 mRNA level was positively correlated with AF duration and the left atrial diameter (P < 0.05 approximately 0.001). CONCLUSION: There is a selective downregulation of TIMP-1 expression along with the upregulation of MMP-9 in AF, which indicates that the disturbance expression of MMP/TIMP system may promote the process of atrial structural remodeling. Enhanced MMP-9 activity may be a molecular mechanism contributing to the dilation of fibrillating human atria.

Individual and Area Level Socioeconomic Status and Its Association with Cognitive Function and Cognitive Impairment (Low MMSE) among Community-Dwelling Elderly in Singapore.

BACKGROUND/AIMS: Neighborhood socioeconomic status (SES) can affect cognitive function. We assessed cognitive function and cognitive impairment among community-dwelling elderly in a multi-ethnic urban low-SES Asian neighborhood and compared them with a higher-SES neighborhood. METHODS: The study population involved all residents aged ≥60 years in two housing estates comprising owner-occupied housing (higher SES) and rental flats (low SES) in Singapore in 2012. Cognitive impairment was defined as <24 on the Mini Mental State Examination. Demographic/clinical details were collected via questionnaire. Multilevel linear regression was used to evaluate factors associated with cognitive function, while multilevel logistic regression determined predictors of cognitive impairment. RESULTS: Participation was 61.4% (558/909). Cognitive impairment was found in 26.2% (104/397) of residents in the low-SES community and in 16.1% (26/161) of residents in the higher-SES community. After adjusting for other sociodemographic variables, living in a low-SES community was independently associated with poorer cognitive function (ß = -1.41, SD = 0.58, p < 0.01) and cognitive impairment (adjusted odds ratio 5.13, 95% CI 1.98-13.34). Among cognitively impaired elderly in the low-SES community, 96.2% (100/104) were newly detected. CONCLUSION: Living in a low-SES community is independently associated with cognitive impairment in an urban Asian society.

Matrix metalloproteinase-9/tissue inhibitors of metalloproteinase-1 expression and atrial structural remodeling in a dog model of atrial fibrillation: inhibition with angiotensin-converting enzyme.

INTRODUCTION: Matrix metalloproteinases and tissue inhibitors of metalloproteinases regulate extracellular matrix turnover in cardiac tissues. However, alteration of matrix metalloproteinases and tissue inhibitors of metalloproteinases during atrial fibrillation is unclear. This study aims to determine (a) the relationship between altered expressions of matrix metalloproteinases and tissue inhibitors of metalloproteinases and atrial structural remodeling; (b) the role of changes in the atrial angiotensin system and in calcium concentration; and (c) the effect of captopril on the expressions of matrix metalloproteinase-9/tissue inhibitors of metalloproteinase-1 and atrial structural remodeling. METHODS: In left atrial tissue samples, the mRNA expression of angiotensin-converting enzyme, matrix metalloproteinase-9, and tissue inhibitors of metalloproteinase-1; the protein expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1; and Ca(2+) concentration and angiotensin II were measured. RESULTS: Compared with controls, dogs under atrial fibrillation showed significantly increased contents of Ca(2+), angiotensin II , and interstitial fibrous tissue (P<.05-.001). The mRNA levels of angiotensin-converting enzyme, matrix metalloproteinase-9, and tissue inhibitors of metalloproteinase-1 were significantly increased as compared with controls (P<.05-.01). The protein level of matrix metalloproteinase-9 was higher, and that of tissue inhibitors of metalloproteinase-1 was lower, in dogs with atrial fibrillation than in controls (P<.01-.001). All findings highlighted above were reversed by treatment with captopril. CONCLUSIONS: Altered expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 contributes to atrial extracellular matrix remodeling and atrial dilatation. Angiotensin-II-mediated intracellular Ca(2+) overload may be the mechanism of altered expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1. Angiotensin-converting enzyme inhibitor treatment may attenuate atrial structural remodeling by normalizing the balance between matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1.