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Augmented efficacy of exogenous extracellular vesicles targeted to injured kidneys

Signal Transduction and Targeted Therapy 2020年第1期5卷 817-819页

作者： Xiao-Jun Chen Kai Jiang Christopher M.Ferguson Hui Tang Xiangyang Zhu Amir lerman lilach o.lerman Division of Nephrology and Hypertension Mayo ClinicRochesterMNUSA Department of Nephrology The Second Xiangya Hospital of Central South UniversityChangshaHunanChina Department of Cardiovascular Diseases Mayo ClinicRochesterMNUSA

Dear Editor,Extracellular vesicles(EVs)derived from mesenchymal stem/stromal cells(MSCs)contain genetic and protein material that stimulate tissue repair and ameliorate injury in recipient *** of particulate MSC-EVs over MSCs in treating kidney disease include better penetration of injured glomerular filtration barrier to access podocytes or tubular ***,systemic EV delivery yields low kidney retention efficiency,limiting their regenerative benefits.1 Previously,we coated adipose tissue-derived(AD)-MSC with antibodies against kidney injury molecule(KIM)‐1(ab-KIM1),a protein upregulated in damaged kidneys.2 Conjugating ab-KIM1 did not impair MSC function but increased their retention and reparative potency in murine renal artery stenosis(RAS).2 We hypothesized that ab-KIM1 conjugation would similarly enhance retention of exogenously delivered EVs in ischemic kidneys and confer superior therapeutic benefits.

关键词： kidney retention sized

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“Nothing burns like the cold”: Cardiovascular disease in frigid zones

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Frigid Zone Medicine 2022年第3期2卷 129-131页

作者： Ben lerman lilach o.lerman School of Medicine Saint George UniversitySt.George’sGrenada Division of Nephrology and Hypertension Mayo ClinicRochester 55905USA

Cardiovascular disease(CVD)is the leading cause of death globally,with the majority of the adult population exposed to multiple traditional or non-traditional CVD risk factors[1].Among the latter,both acute and lengthy exposures to low temperatures can increase cardiovascular risk,particularly in individuals with an underlying *** link between CVD and cold weather is reflected in a well-documented peak in cardiovascular deaths during the winter months[2].For example,investigators in Germany found that a 10°C decrease in 5-day average temperature was associated with a 1.10 relative risk of myocardial infarction[3],while in China each 1°C decrease in temperature during a cold wave increased the mortality risk from myocardial infarction by 1.82%[4].

关键词： cardiovascular acute mortality

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Micro-RNAs Regulate Metabolic Syndrome-induced Senescence in Adipose Tissue-derived Mesenchymal Stem Cells of through P16/MAPK Pathway

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临床医学工程 2017年第S1期24卷 48-48页

作者： Yu Meng Alfonso Eirin lilach o.lerman Divisions of Nephrology and Hypertension Mayo Clinic Department of Nephrology the First Hospital Affiliated to Jinan University

Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk ***,adipose tissue-derived MSCs from pigs with the metabolic syndrome(Met S)show decreased vitality.A growing number of micro RNAs(mi RNAs)are recognized as key modulators of senescence,but their role in regulating senescence in MSC in Mets is *** tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)*** MSCs were collected from swine abdominal adipose tissue after 16 weeks of Lean or obese diet(n=6 each).Next-generation mi RNA sequencing(mi RNA-seq)was performed to identify mi RNAs up-or down-regulated in Met S-MSC compare to *** pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology *** senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase *** addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi *** Senescence biomarkers were significantly elevated in Met S *** found the 7 upregulated mi RNAs,including mi R-27b,and 3 downregulated mi RNAs in Met S-MSCs,which regulate 35 SA genes,particularly MAPK *** of mi R-27b in cultured MSC downregulated p16 and MARP3 *** Met S modulate MSC expression of SA-mi RNAs that may play the role in modulating their senescence,and the p16 pathway in Met S-MSCs senescence is the primary pathway.

关键词： Mesenchymal stem cells Senescence Micro RNA Metabolic syndrome

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Long-term outcomes after fractional flow reserve-guided percutaneous coronary intervention in patients with severe coronary stenosis

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Journal of Geriatric Cardiology 2019年第4期16卷 329-337页

作者： Ying-Hua ZHANG Jing LI Andreas J. Flammer Yoshiki Matsuo Moo-Sik Lee Ryan J. Lennon Malcolm R. Bell David R. Holmes John F. Bresnahan Charanjit S. Rihal lilach o. lerman Amir lerman Division of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Division of Cardiovascular Diseases Mayo ClinicRochesterUSA Cardiovascular Center CardiologyUniversity Hospital ZurichSwitzerland Department of Preventive Medicine College of Medicine Konyang UniversityDaejeonSouth Korea Biomedical Statistics Mayo ClinicRochesterUSA Division of Nephrology and Hypertension Mayo ClinicRochesterUSA

objective To explore the safety and efficacy of FFR-guided percutaneous coronary intervention (PCI) in vessels with severe diameter stenosis. Methods & Results of 1090 patients undergoing fractional flow reserve (FFR) assessment from 2002 to 2009,we identified 167 patients in whom FFR was measured in at least one 70%–89% stenotic lesion. These patients were subdivided into an FFR-defer group (n = 49) if PCI was deferred (FFR > 0.80),and an FFR-perform group (n = 118) if PCI was performed (FFR ≤ 0.80). Comparatively,an additional 1176 patients undergoing PCI in at least one lesion with 70%–89% stenosis but without measurement of FFR served as a control (angiography- guided) group. Clinical outcomes were compared during a median follow-up of 49.0 months. The 5-year Kaplan-Meier estimated revascularization rates were 16% in the FFR-defer group and 33% in the FFR-perform group (P = 0.046). The incidence of major adverse cardiac events were comparable in these two groups (HR = 0.82,95% CI: 0.37–1.82,P = 0.63). The number of stents placed was significantly lower in the FFR-guided group (0.9 ± 0.8 vs. 1.4 ± 0.8,P onclusions Functional revascularization for lesions with visually severe stenosis is clinically safe and associated with fewer stents use. This study suggests that extending the use of FFR to more severe coronary lesions may be reasonable.

关键词： Fractional flow reserve outcome Percutaneous coronary intervention Severe stenosis Stent

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