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Peter Jones

Publications and source records attributed to Peter Jones.

58 records · Page 4Linked to original sources

Involvement of matrix metalloproteinases and tenascin-C in elastin calcification.

Elastin degeneration and calcification occur in many cardiovascular diseases, including medial arterial elastocalcinosis, atherosclerosis, and bioprosthetic heart valve mineralization. In the present study, we tested the hypothesis that the onset and progression of elastin-oriented calcification is associated with matrix remodeling and elastin degradation events. We studied whether aluminum ions inhibit elastin calcification by reducing elastin degradation and altering remodeling events. Subdermal implantation of pure elastin in juvenile rats resulted in a time-dependent calcification of elastin, reaching high levels 21 days after implantation. In situ hybridization showed that elastin calcification was associated with an up-regulation of matrix metalloproteinase (MMP) mRNA expression, specifically MMP-9 and MMP-2. Gelatin zymography demonstrated increased MMP-9 and MMP-2 enzyme activities in early stages of elastin calcification. Calcified elastin displayed a time-dependent pattern of tenascin-C (TN-C) and alkaline phosphatase (AP) expression. Pretreatment of pure elastin with aluminum ions prior to implantation resulted in complete inhibition of elastin calcification. Aluminum ion binding to elastin was found to protect elastin against MMP-mediated degradation in vitro. Noncalcified, explanted aluminum-pretreated elastin exhibited reduced activities of MMPs. TN-C expression in elastin implants exhibited a time-dependent pattern that was also affected by pretreatment of elastin with aluminum ions. In conclusion, elastin calcification is accompanied by matrix remodeling events, and the efficacy of aluminum pretreatment in inhibiting elastin calcification may be related in part to its effects on elastin remodeling.

Alkaline Phosphatase↗

Quantifying the effect of applying the NCEP ATP III criteria in a managed care population treated with statin therapy.

OBJECTIVE: Revised treatment goals suggested by the third report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) represent a challenge to both physicians and the health care industry. We sought to quantify the impact of these changes in a large managed care population being treated with statin therapy. METHODS: Using data collected from a retrospective chart review of 1,962 managed care enrollees who received statin drug therapy between February 2001 and August 2001, we quantified the low-density lipoprotein cholesterol (LDL-C) goals and goal attainment of this population according to both the NCEP ATP II and ATP III criteria and further identified independent predictors of ATP III goal attainment using multivariable logistic regression modeling. RESULTS: Overall, 21.1% (n = 414) of statin patients moved to a more stringent LDL-C goal when ATP III criteria were applied over ATP II. Substituting ATP III criteria for ATP II criteria resulted in a 6.8% decrease in the percentage of participants who had their most recent LDL-C value below the suggested goal, from 59.8% under ATP II to 53.0% under ATP III. Persons with existing coronary heart disease, diabetes, obesity, and stroke or transient ischemic attack were all less likely to meet the suggested NCEP ATP III LDL-C goal. CONCLUSION: Taking into account the revised risk stratification of the ATP III guidelines and the lack of LDL-C goal attainment in patients currently taking statins, there will be an increase in the number of statin patients who require dose or agent adjustment, combination therapy, or compliance counseling to achieve their lower LDL-C goal.

Adult↗