The role of DNA damage and repair in atherosclerosis: A review

Shah, Nilpa; Mahmoudi, Michael

doi:10.1016/j.yjmcc.2015.07.005

Cited by 49 publications

(35 citation statements)

References 186 publications

(144 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This modulation of cellular signaling may have pro-apoptotic, antiproliferative, anti-invasive, and radiosensitizing effects [23,135,136]. Statins may also play a protective role against DNA damage which is a key factor in pathophysiology of both atherosclerosis and cancer [141]. Recent studies have shown that statins slightly increase the incidence of new-onset T2DM [142, 143] and the effect varies as per the dosage and type used [142].…”

Section: Joint Pharmacologic Prevention For Cvd and Cancermentioning

confidence: 99%

Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention

et al. 2017

View full text Add to dashboard Cite

Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide. Strategies to improve their treatment and prevention are global priorities and major focus of World Health Organization’s joint prevention programs. Emerging evidence suggests that modifiable risk factors including diet, sedentary lifestyle, obesity and tobacco use are central to the pathogenesis of both diseases and are reflected in common genetic, cellular, and signaling mechanisms. Understanding this important biological overlap is critical and may help identify novel therapeutic and preventative strategies for both disorders. In this review, we will discuss the shared genetic and molecular factors central to CVD and cancer and how the strategies commonly used for the prevention of atherosclerotic vascular disease can be applied to cancer prevention.

show abstract

Section: Joint Pharmacologic Prevention For Cvd and Cancermentioning

confidence: 99%

Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Apoptosis of vascular smooth muscle cells (SMCs) is the major driving force of atherosclerotic plaque destabilization (3), and preventing plaque SMC apoptosis is a promising antiatherosclerotic strategy (4). DNA‐damaging agents are potent inducers of cell death by apoptosis (5), and enhanced DNA damage and/or suppression of DNA repair pathways are now recognized as crucial factors in the initiation and progression of atherosclerosis (6, 7). In the base excision repair pathway, apurinic/apyrimidinic (AP) sites caused by oxidation produce ssDNA breaks and are removed from the genome (8).…”

mentioning

confidence: 99%

Nuclear complex of glyceraldehyde‐3‐phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant‐induced cell death

Hou¹,

Snarski²,

Higashi³

et al. 2017

FASEB j.

View full text Add to dashboard Cite

Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMCs that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated HO-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis. Ape1 down-regulation reversed the resistance of GAPDH-overexpressing cells to DNA damage and apoptosis, which indicated that Ape1 is indispensable for GAPDH-dependent protective effects. GAPDH bound Ape1 in the SMC nucleus, and blocking (or oxidation) of GAPDH active site cysteines suppressed GAPDH/Ape1 interaction and potentiated apoptosis. GAPDH up-regulated Ape1 a transcription factor homeobox protein Hox-A5-dependent mechanism. GAPDH levels were reduced in atherosclerotic plaque SMCs, and this effect correlated with oxidative stress and SMC apoptosis. Thus, we demonstrated that nuclear GAPDH/Ape1 interaction preserved Ape1 activity, reduced DNA damage, and prevented SMC apoptosis. Suppression of SMC apoptosis by maintenance of nuclear GAPDH/Ape1 interactions may be a novel therapy to increase atherosclerotic plaque stability.-Hou, X., Snarski, P., Higashi, Y., Yoshida, T., Jurkevich, A., Delafontaine, P., Sukhanov, S. Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death.

show abstract

“…However, INPP4B knockdown sensitized KG-1 to cytarabine, and p-H2AX expression also sharply increased after INPP4B knockdown, indicating that INPP4B knockdown is correlated with the increase in DSBs formation. It has been established that DSBs formation is subsequently accompanied by DSB repair [25], and the loss of p-H2AX has been shown to closely correlate to DSB repair [26]. To further understand how INPP4B influences the DSBs formation, whether the enhanced DSBs formation after INPP4B knockdown could be attributed to lower DNA damage repair, we next targeted the loss of p-H2AX expression.…”

Section: Discussionmentioning

confidence: 99%

INPP4B-mediated DNA repair pathway confers resistance to chemotherapy in acute myeloid leukemia

Wang

et al. 2016

Tumor Biol.

View full text Add to dashboard Cite

INPP4B has been recently shown to be a poor prognostic marker and confer chemo- or radio-resistance in AML cells, whereas, the underlying mechanisms remain unclear. Herein, we aimed to explore the possible mechanisms mediated the resistance to chemotherapy in AML. We found that INPP4B-mediated resistance to genotoxic drug, cytarabine, was accompanied by lower p-H2AX accumulation in KG-1 cells, and INPP4B knockdown evidently sensitized KG-1 cells to cytarabine, meanwhile, p-H2AX expression was increased dramatically. Then, we observed that INPP4B knockdown inhibited the loss of p-H2AX expression after cytarabine removal in INPP4B-silenced KG-1 cells, whereas, in control KG-1 cells, the expression of p-H2AX was reduced in a time-dependent manner. Next, INPP4B knockdown can significantly downregulate ATM expression and subsequently inhibit the activation of ATM downstream targets of p-ATM, p-BRCA1, p-ATR, and p-RAD51. Furthermore, nuclear localization of p65 was inhibited after INPP4B knockdown, and reactivation of p65 can rescue the INPP4B knockdown-induced inhibition of ATM, p-ATM, p-BRCA1, p-ATR, and p-RAD51. Finally, INPP4B expression was positively correlated with ATM expression in AML cells, both INPP4B knockdown and KU55933 can significantly sensitize primary myeloid leukemic cells to cytarabine treatment.Collectively, these data suggest that enhanced ATM-dependent DNA repair is involved in resistance to chemotherapy in INPP4B AML, which could be mediated by p65 nuclear translocation, combination chemotherapy with INPP4B or DNA repair pathway inhibition represents a promising strategy in INPP4B AML.

show abstract

The role of DNA damage and repair in atherosclerosis: A review

Cited by 49 publications

References 186 publications

Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention

Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention

Nuclear complex of glyceraldehyde‐3‐phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant‐induced cell death

INPP4B-mediated DNA repair pathway confers resistance to chemotherapy in acute myeloid leukemia

Contact Info

Product

Resources

About