scholarly journals Why is coronary collateral growth impaired in type II diabetes and the metabolic syndrome?

2012 ◽  
Vol 57 (5-6) ◽  
pp. 179-186 ◽  
Author(s):  
Petra Rocic
Keyword(s):  
Metabolic Syndrome ◽  
Type Ii Diabetes ◽  
Type Ii ◽  
Coronary Collateral ◽  
The Metabolic Syndrome ◽  
Collateral Growth ◽  
Coronary Collateral Growth

scholarly journals Angiotensin type I receptor blockade in conjunction with enhanced Akt activation restores coronary collateral growth in the metabolic syndrome

2011 ◽  
Vol 300 (5) ◽  
pp. H1938-H1949 ◽  
Author(s):  
Rashmi Jadhav ◽  
Tracy Dodd ◽  
Erika Smith ◽  
Erin Bailey ◽  
Angelo L. DeLucia ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Transduction Efficiency ◽  
Type I ◽  
Flow Measurements ◽  
Akt Activation ◽  
Coronary Collateral ◽  
The Metabolic Syndrome ◽  
Collateral Growth ◽  
Coronary Collateral Growth ◽  
Angiotensin Type

We have previously demonstrated that Akt was required for repetitive ischemia (RI)-induced coronary collateral growth (CCG) in healthy rats but was not activated by RI in the metabolic syndrome (JCR:LA-cp rats) where CCG was impaired. Here we hypothesized that failure of angiotensin type I receptor (AT1R) blockers to restore Akt activation is a key determinant of their inability to completely restore CCG in the metabolic syndrome. Therefore, we investigated whether adenovirus-mediated delivery of constitutively active Akt (MyrAkt-Adv) in conjunction with AT1R blockade (candesartan) was able to restore RI-induced CCG in JCR:LA-cp rats. Successful myocardial MyrAkt-Adv delivery was confirmed by a >80% transduction efficiency and an approximately fourfold increase in Akt expression and activation. CCG was assessed by myocardial blood flow measurements in the normal and collateral-dependent zones. MyrAkt-Adv alone significantly increased RI-induced CCG in JCR:LA-cp rats (∼30%), but it completely restored CCG in conjunction with administration of candesartan. In contrast, dominant negative Akt (DN-Akt-Adv) reversed the beneficial effect of candesartan on CCG in JCR:LA-cp rats. We conclude that optimal restoration of coronary collateral growth in JCR:LA-cp rats requires a combination of AT1R blockade with constitutive Akt activation. These findings may carry implications for metabolic syndrome patients in need of coronary revascularization.

Abstract P129: 20-HETE Antagonist, 20-SOLA, Restores Coronary Collateral Growth in the Metabolic Syndrome

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Amanda A Soler ◽  
Brenda Hutcheson ◽  
Manuel A Devila-Molina ◽  
Ian Hunter ◽  
Victor G Garcia ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Arachidonic Acid Metabolite ◽  
Collateral Flow ◽  
Rt Pcr ◽  
Coronary Collateral ◽  
The Metabolic Syndrome ◽  
Cardiovascular Tissues ◽  
Hypertensive Animal ◽  
Collateral Growth ◽  
Coronary Collateral Growth

We have previously shown that transient and repetitive ischemia-induced (RI) coronary collateral growth (CCG) was severely impaired in a metabolic syndrome rat model (JCR rat). Levels of 20-hydroxyeicosatetraeonic acid (20-HETE), a cytochrome (CYP)-derived arachidonic acid metabolite are greatly elevated in hypertensive animal models and loosely associated with obesity in humans, but its levels in metabolic syndrome, especially in cardiovascular tissues, as well as its possible involvement in the regulation of collateral growth are unknown. In rats, CYP4A1 is the major enzyme responsible for the production of 20-HETE. In this study, we demonstrated that cardiac CYP4A1 expression (RT-PCR, Western blot and immunohistochemistry) and 20-HETE levels were markedly (10-fold) elevated in JCR vs. Sprague-Dawly (SD) rats in response to RI. Importantly, administration of an antagonist of 20-HETE, 20-SOLA, completely restored CCG in JCR rats (collateral flow was 86±1% of that in the normal zone (JCR+SOLA) vs. 21±2% (JCR) vs. 84±5% (SD), p<0.05). We conclude that 20-HETE is an important modulator of CCG in the metabolic syndrome where its myocardial tissue levels are highly elevated.

scholarly journals miR-21-mediated decreased neutrophil apoptosis is a determinant of impaired coronary collateral growth in metabolic syndrome

2015 ◽  
Vol 308 (11) ◽  
pp. H1323-H1335 ◽  
Author(s):  
Rebecca Hutcheson ◽  
Russell Terry ◽  
Brenda Hutcheson ◽  
Rashmi Jadhav ◽  
Jennifer Chaplin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Cytochrome C ◽  
Stress Generation ◽  
Neutrophil Apoptosis ◽  
Cytochrome C Release ◽  
Coronary Collateral ◽  
Sd Rats ◽  
Collateral Growth ◽  
Coronary Collateral Growth

Coronary collateral growth (CCG) is impaired in metabolic syndrome. microRNA-21 (miR-21) is a proproliferative and antiapoptotic miR, which we showed to be elevated in metabolic syndrome. Here we investigate whether impaired CCG in metabolic syndrome involved miR-21-mediated aberrant apoptosis. Normal Sprague-Dawley (SD) and metabolic syndrome [J. C. Russel (JCR)] rats underwent transient, repetitive coronary artery occlusion [repetitive ischemia (RI)]. Antiapoptotic Bcl-2, phospho-Bad, and Bcl-2/Bax dimers were increased on days 6 and 9 RI, and proapoptotic Bax and Bax/Bax dimers and cytochrome- c release concurrently decreased in JCR versus SD rats. Active caspases were decreased in JCR versus SD rats (∼50%). Neutrophils increased transiently on day 3 RI in the collateral-dependent zone of SD rats but remained elevated in JCR rats, paralleling miR-21 expression. miR-21 downregulation by anti-miR-21 induced neutrophil apoptosis and decreased Bcl-2 and Bcl-2/Bax dimers (∼75%) while increasing Bax/Bax dimers, cytochrome- c release, and caspase activation (∼70, 400, and 400%). Anti-miR-21 also improved CCG in JCR rats (∼60%). Preventing neutrophil infiltration with blocking antibodies resulted in equivalent CCG recovery, confirming a major role for deregulated neutrophil apoptosis in CCG impairment. Neutrophil and miR-21-dependent CCG inhibition was in significant part mediated by increased oxidative stress. We conclude that neutrophil apoptosis is integral to normal CCG and that inappropriate prolonged miR-21-mediated survival of neutrophils plays a major role in impaired CCG, in part via oxidative stress generation.

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