Browsing by Author "Kumar, Praveen"

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    Characteristics of extremely low birth weight infant survivors with unimpaired outcomes at 30 months of age
    (Springer Nature, 2013) Kumar, Praveen; Shankaran, Seetha; Ambalavanan, Namasivayam; Kendrick, Douglas E.; Pappas, Athina; Vohr, Betty R.; Poindexter, Brenda B.; Das, Abhik; Higgins, Rosemary D.; NICHD Neonatal Research Network; Pediatrics, School of Medicine
    Objective: To evaluate characteristics of unimpaired outcome in extremely low-birth-weight (ELBW) survivors. Study design: ELBW infants (n=714) with 30 months' assessments were analyzed. Logistic regression was used to develop a model for the binary outcome of unimpaired versus impaired outcome. Result: Thirty-three percent of infants had an unimpaired outcome. Seventeen percent of ELBW survivors had a Bayley II Mental Developmental Index score of ≥ 101 and 2% had a score of ≥ 116. Female gender, use of antenatal steroids (ANS), maternal education ≥ high school and the absence of major neonatal morbidities were independent predictors of unimpaired outcome. The likelihood of an unimpaired outcome in the presence of major neonatal morbidities was higher in infants exposed to ANS. Conclusion: The majority of unimpaired ELBW survivors had cognitive scores shifted toward the lower end of the normal distribution. Exposure to ANS was associated with higher likelihood of an unimpaired outcome in infants with major neonatal morbidities.
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    Targeting LOXL2 for cardiac interstitial fibrosis and heart failure treatment
    (SpringerNature, 2016-12-14) Yang, Jin; Savvatis, Konstantinos; Kang, Jong Seok; Fan, Peidong; Zhong, Hongyan; Schwartz, Karen; Barry, Vivian; Mikels-Vigdal, Amanda; Karpinski, Serge; Kornyeyev, Dmytro; Adamkewicz, Joanne; Feng, Xuhui; Zhou, Qiong; Shang, Ching; Kumar, Praveen; Phan, Dillon; Kasner, Mario; Lopez, Begona; Diez, Javier; Wright, Keith C.; Kovacs, Roxanne L.; Chen, Peng-Sheng; Quertermous, Thomas; Smith, Victoria; Yao, Lina; Tschope, Carsten; Chang, Ching-Pin; Department of Medicine, IU School of Medicine
    Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions. Loxl2 stimulates cardiac fibroblasts through PI3K/AKT to produce TGF-β2, promoting fibroblast-to-myofibroblast transformation; Loxl2 also acts downstream of TGF-β2 to stimulate myofibroblast migration. In diseased human hearts, LOXL2 is upregulated in cardiac interstitium; its levels correlate with collagen crosslinking and cardiac dysfunction. LOXL2 is also elevated in the serum of heart failure (HF) patients, correlating with other HF biomarkers, suggesting a conserved LOXL2-mediated mechanism of human HF.