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DiscussionLet's talk about it: The science of itVitamin A and Coronary Artery Dis …

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Vitamin A and Coronary Artery Disease

#1 · November 21, 2018, 11:17 am

In Dr. Gundry's book, he mentions - as a heart surgeon - that when he opens people up, they have tonnes of fat over their heart. This is well known.

I think there is always a reason for everything the body does. So why would it deposit tonnes of fat around the heart?

Since vitamin A is fat soluble, could it be creating a protective reservoir? Could retinoic acid be causing inflammation in the artery wall, dragging in calcium and necessitating the deposition of antioxidant cholesterol, causing the plaque?

I wanted to find a study analysing the the retinol concentration of the pericardial fat, but I couldn't. I did find this, however:

Coronary artery disease is associated with higher epicardial retinol-binding protein 4 (RBP4) and lower glucose transporter (GLUT) 4 levels in epicardial and subcutaneous adipose tissue.

Higher amounts of retinol binding protein suggests higher amounts of retinol. Could this be the cause of the adiposity?

#2 · December 8, 2018, 10:58 pm

Quote from Zach G on December 8, 2018, 10:58 pm
I came across this study that was published the day after your post. I have yet to read much beyond the abstract...

Early inhibition of endothelial retinoid uptake upon myocardial infarction restores cardiac function and prevents cell, tissue, and animal death

https://www.jmmc-online.com/article/S0022-2828(18)31193-3/fulltext

Retinoids in the myocardial infraction zone have adverse effects on MI outcome

Inhibition of cellular retinoid uptake reduces cell death under hypoxic conditions.

Endothelial cell death enhances cardiomyocyte death under hypoxic conditions.

5′-Methoxyleoligin inhibits cellular retinoid uptake by binding to STRA6.

5′-Methoxyleoligin protects from hypoxia and ATRA-enhanced cell death in MI.

Abstract

Physiologically, following myocardial infarction (MI), retinoid levels elevate locally in the infarcted area. Whereas therapeutic systemic application of retinoids was shown to reduce the progression of ventricular dilatation and the onset of heart failure, the role of acute physiologically increased retinoids in the infarction zone is unknown to date. To reveal the role of local retinoids in the MI zone is the central aim of this study. Using human cell culture and co-culture models for hypoxia as well as various assays systems, lentivirus-based transgene expression, in silico molecular docking studies, and an MI model in rats, we analysed the impact of the retinoid all-trans retinoic acid (ATRA) on cell signalling, cell viability, tissue survival, heart function, and MI-induced death in rats. Based on our results, ATRA-mediated signalling does aggravate the MI phenotype (e.g. 2.5-fold increased mortality compared to control), whereas 5'-methoxyleoligin (5ML), a new agent which interferes with ATRA-signalling rescues the ATRA-dependent phenotype. On the molecular level, ATRA signalling causes induction of TXNIP, a potent inhibitor of the physiological antioxidant thioredoxin (TRX1) and sensitizes cells to necrotic cell death upon hypoxia. 5ML-mediated prevention of ATRA effects were shown to be based on the inhibition of cellular ATRA uptake by interference with the cholesterol (and retinol) binding motif of the transmembrane protein STRA6. 5ML-mediated inhibition of ATRA uptake led to a strong reduction of ATRA-dependent gene expression, reduced ROS formation, and protection from necrotic cell death. As 5ML exerted a cardioprotective effect, also independent of its inhibition of cellular ATRA uptake, the agent likely has another cardioprotective property, which may rely on the induction of TRX1 activity. In summary, this is the first study to show i) that local retinoids in the early MI zone may worsen disease outcome, ii) that inhibition of endothelial retinoid uptake using 5ML may constitute a novel treatment strategy, and iii) that targeting endothelial and myocardial retinoid uptake (e.g. via STRA6 inhibition) may constitute a novel treatment target in acute MI.

I came across this study that was published the day after your post. I have yet to read much beyond the abstract...

Early inhibition of endothelial retinoid uptake upon myocardial infarction restores cardiac function and prevents cell, tissue, and animal death

https://www.jmmc-online.com/article/S0022-2828(18)31193-3/fulltext

Retinoids in the myocardial infraction zone have adverse effects on MI outcome
Inhibition of cellular retinoid uptake reduces cell death under hypoxic conditions.
Endothelial cell death enhances cardiomyocyte death under hypoxic conditions.
5′-Methoxyleoligin inhibits cellular retinoid uptake by binding to STRA6.
5′-Methoxyleoligin protects from hypoxia and ATRA-enhanced cell death in MI.

Abstract

Physiologically, following myocardial infarction (MI), retinoid levels elevate locally in the infarcted area. Whereas therapeutic systemic application of retinoids was shown to reduce the progression of ventricular dilatation and the onset of heart failure, the role of acute physiologically increased retinoids in the infarction zone is unknown to date. To reveal the role of local retinoids in the MI zone is the central aim of this study. Using human cell culture and co-culture models for hypoxia as well as various assays systems, lentivirus-based transgene expression, in silico molecular docking studies, and an MI model in rats, we analysed the impact of the retinoid all-trans retinoic acid (ATRA) on cell signalling, cell viability, tissue survival, heart function, and MI-induced death in rats. Based on our results, ATRA-mediated signalling does aggravate the MI phenotype (e.g. 2.5-fold increased mortality compared to control), whereas 5'-methoxyleoligin (5ML), a new agent which interferes with ATRA-signalling rescues the ATRA-dependent phenotype. On the molecular level, ATRA signalling causes induction of TXNIP, a potent inhibitor of the physiological antioxidant thioredoxin (TRX1) and sensitizes cells to necrotic cell death upon hypoxia. 5ML-mediated prevention of ATRA effects were shown to be based on the inhibition of cellular ATRA uptake by interference with the cholesterol (and retinol) binding motif of the transmembrane protein STRA6. 5ML-mediated inhibition of ATRA uptake led to a strong reduction of ATRA-dependent gene expression, reduced ROS formation, and protection from necrotic cell death. As 5ML exerted a cardioprotective effect, also independent of its inhibition of cellular ATRA uptake, the agent likely has another cardioprotective property, which may rely on the induction of TRX1 activity. In summary, this is the first study to show i) that local retinoids in the early MI zone may worsen disease outcome, ii) that inhibition of endothelial retinoid uptake using 5ML may constitute a novel treatment strategy, and iii) that targeting endothelial and myocardial retinoid uptake (e.g. via STRA6 inhibition) may constitute a novel treatment target in acute MI.

#3 · December 8, 2018, 11:43 pm

Another interesting study:

Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats.

...RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

#4 · December 9, 2018, 7:26 am

Very interesting! Thanks for the posts!

Vitamin A and Coronary Artery Disease

Coronary artery disease is associated with higher epicardial retinol-binding protein 4 (RBP4) and lower glucose transporter (GLUT) 4 levels in epicardial and subcutaneous adipose tissue.

Coronary artery disease is associated with higher epicardial retinol-binding protein 4 (RBP4) and lower glucose transporter (GLUT) 4 levels in epicardial and subcutaneous adipose tissue.

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