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 length...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 CVD.The 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].展开更多
Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,adipose tissue-derived MSCs from pigs with the metabolic syndrome...Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,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 unclear.We tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)genes.Methods 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 Lean-MSCs.Functional pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology analysis.MSC senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase activity.In addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi R-27b.Results Senescence biomarkers were significantly elevated in Met S MSC.We 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 signaling.Inhibition of mi R-27b in cultured MSC downregulated p16 and MARP3 genes.Conclusions 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.展开更多
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 cells.Advantages of particul...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 cells.Advantages of particulate MSC-EVs over MSCs in treating kidney disease include better penetration of injured glomerular filtration barrier to access podocytes or tubular cells.However,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.展开更多
基金supported by National Institutes of Health grant numbers DK120292,DK122734,HL158691,and AG062104.
文摘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 CVD.The 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].
基金Guangdong Provincial Center for clinical engineering of blood purification(507204531040)
文摘Background Mesenchymal stem cells(MSC)constitute an important repair system,but may be impaired by exposure to cardiovascular risk factors.Consequently,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 unclear.We tested the hypothesis that Met S upregulates in MSC expression of mi RNAs that can serve as post-transcriptional regulators of senescence-associated(SA)genes.Methods 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 Lean-MSCs.Functional pathway analysis of SA genes targeted by mi RNAs was performed using gene ontology analysis.MSC senescence was evaluated by p16 and p21 immunoreactivity,H2AX protein expression,and SA-beta-Galactosidase activity.In addition,gene expression of p16,p21,MAPK3,and MAPK14 was studied after inhibition of SA-mi R-27b.Results Senescence biomarkers were significantly elevated in Met S MSC.We 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 signaling.Inhibition of mi R-27b in cultured MSC downregulated p16 and MARP3 genes.Conclusions 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.
基金supported by NIH Grants Numbers DK122734,DK102325,and DK120292.
文摘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 cells.Advantages of particulate MSC-EVs over MSCs in treating kidney disease include better penetration of injured glomerular filtration barrier to access podocytes or tubular cells.However,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.
