Into the Heart

Estrogen Receptors & The Heart Muscle

The benefits of estrogen replacement therapy in reducing risk factors for cardiovascular disease accounts for about 50%. This implies that additional mechanisms must exist whereby estrogen exerts a cardioprotective action. Previous studies have concentrated mostly on the vascular effects (blood vessels) of estrogen, but cardio-protection by estrogen is not necessarily restricted to the vasculature.

The myocardium is the middle layer of the musclar tissue of the heart. Recent research indicates the benefits of estrogen gradually shift from the vascular system to the myocardium. This view is supported by the fact that functional estrogen receptors have been detected in the myocardium. These receptors regulate the expression of many genes including connexin 43 and heavy chain a-myosin (major contractile proteins in the heart).

Estrogen has also been shown to be a calcium channel blocker, possibly providing additional cardiovascular protection.

A calcium channel blocker (CCB) is a drug that blocks the entry of calcium into the muscle cells of the heart and the arteries. It is the entry of calcium into these cells that causes the heart to contract and arteries to narrow. By blocking the entry of calcium, calcium channel blocker decrease the contraction of the heart and dilate (widen) the arteries.

By dilating the arteries, CCBs reduce the pressure in the arteries. This makes it easier for the heart to pump blood, and, as a result, the heart needs less oxygen. By reducing the heart's need for oxygen, CCBs prevent or relieve angina.

CCBs also are used for treating high blood pressure because of their blood pressure-lowering effects. CCBs also slow the rate at which the heart beats and are therefore used for treating certain abnormal heart rhythms such as atrial fibrillation.

Source:
Myocardial antioxidant and oxidative stress changes due to sex hormones.
Braz J Med Biol Res, September 2002, Volume 35(9) 1075-1081

Oestrogen as a calcium channel blocker.
Eur Heart J. 1996 Aug;17 Suppl D:27-31.

Medicinenet.com

Estrogen Replacement and Cardiovascular Wellness

Cardiovascular disease remains a major cause of death among postmenopausal women. After menopause, atherogenesis is promoted by a number of metabolic and vascular changes.

Atherogenesis is the formation of fatty deposits in the artery. These fatty deposits can become inflammed, and enlarged which then creates blockages in the coronary & cerebral arteries. Occluded (blocked) arteries reduce the ability of the heart and brain to receive oxygen and nutrients (ischemia). As such, heart and brain cells are not functioning at full capacity.

A multitude of observational clinical studies concluded that estrogen replacement therapy (ERT) reduces cardiovascular risk by approximately 50%.  Yet, estrogen's favorable effects on the lipid profile explains only 30-50% of the overall observed risk reduction. It is now understood that estrogen has anti-atherogenic properties through both lipid (fat/cholesterol)and non-lipid mechanisms.

Estrogens induce favorable changes on lipids and lipoproteins, partly by increasing HDL-cholesterol and decreasing both LDL-cholesterol and lipoprotein (a). HDL is the cholesterol that transports fats away from the arteries to the liver for removal. HDL also helps protect LDL cholesterol from becoming oxidized (rancid). A high HDL concentration is cardio-protective.

Non-lipid mechanisms of estrogens cardio-protective actions include decreasing insulin resistance, serum fibrinogen, factor VII and plasminogen activator inhibitor-1 (PAI-1).

Studies indicate estrogen helps maintain endothelial cell integrity, decreases expression of adhesion molecules, lowers systemic blood pressure, promotes vasodilatation, decreases platelet aggregability, inhibits vascular smooth muscle cell proliferation, possesses potent antioxidant and calcium antagonist activities, inhibits adrenergic responses and downregulate (lessen) platelet and monocyte reactivity.

More recent reports are linking estrogen to the renin-angiotensin system, relaxin, serotonin and homocysteine.

Keep in mind, the vascular effects of estrogen replacement (17B-estradiol) depends on the timing, initiation, type and mode of administration (oral or transdermal).

Source:
Gynecol-Endocrinol. 1998 Feb; 12(1): 43-59
Author: Nasr, A : Breckwoldt, M 

A Bit About Estrogen Receptors ER-a and ER-b

Estrogen has significant actions for the preservation of bone, blood vessel integrity, and contributes to brain function and the modulation of immunity. Estrogen also affects central nervous system functions and the neuroendocrine-gonadal axis in both sexes.

Two isoforms of nuclear estrogen receptors have been identified, cloned and characterized: ER-a and ER-b. They are distinct proteins encoded by separate genes located on different chromosomes.

The cDNA for the human ER-a was cloned in 1985. The discovery of estrogen receptor ER-b was reported in 1996.

ER-a exists as the predominant receptor in most classic estrogen target organs. A clear role for ER-b has been established in the ovary, cardiovascular system, and brain as well as in several animal models of inflammation including arthritis, endometriosis, inflammatory bowel disease, and sepsis (infection).

ER-a and ER-b proteins bind 17B-estradiol (E2) with nearly equal affinity and exhibit a very similar binding profile for a number of natural and synthetic ligands. 

Ligands are molecules, either synthetic or of natural origin, that  bind to certain proteins. In the case of natural ligands, such as hormones, or neurotransmitters the proteins they bind are called receptors.

Isoflavone phytoestrogens daidzein and genistein are well known ER-b selective compounds. They bind and activate human ER-a and ER-b with an up to 100 fold stronger activation of ER-b.

Source:
Experimental Dermatology 2006 pgs 85-87
Verdier-Sevrain et al

Mechanism of Estrogenic Vascular Protection
Am J Physiology  Heart Circ Physiol 209: H507-H508, 2006

Cell localization, Physiology, and Nongenomic Actions of Estrogen Receptors
Ellis R. Levin
J Appl Physiol 91: 1860-1867, 2001

Salmon, Vitamin B5 and the Nervous Control of the Heart.

The sympathetic and para-sympathetic components of the autonomic nervous system work in direct opposition to one another to regulate the heart.
The Sympathetic Nervous System innervates the heart through the cardiac plexus (a network of nerves at the base of the heart).
The primary neurotransmitter of the SNS is norepinephrine.
Norepinephrine increases heart rate and contractility force.

The Para-sympathetic Nervous System innervates the heart through the vagus nerve (the 10th cranial nerve).
The primary neurotransmitter of the PNS is acetylcholine.
Acetylcholine slows the heart rate and atrioventricular conduction.

Vitamin B5 (pantothenic acid), is a water-soluble vitamin involved in the Kreb’s cycle of energy production and is also needed to make the neurotransmitter acetylcholine. Vitamin B5 is also essential in producing, transporting and releasing energy from fats.

Liver, kidney, salmon and brown rice have high concentrations of Vitamin B5. Brown rice with wild rice compliments salmon patties and broiled salmon.

Sources:
www.cvphysiology.com

Physicians Desk Reference for Nutritional Supplements
www.pdr.com search pantothenic acid, Vitamin B5

Red Wine Lessens Arterial Build-up

The intima layer of the artery lies just below the endothelium.  Smooth muscle cells normally lie in the media layer of the artery.  Smooth muscle cells are responsible for maintaining vascular tone.  During the atherosclerosis process smooth muscle cells along with macrophages (foam cells) proliferate in the intima layer of the artery.

The process of migration, division and synthesis is referred to as intimal proliferation (buildup) and causes thickening of the intima.  Smooth muscle cells from the media move (migrate) into the intima, these smooth muscle cells reproduce themselves (divide) and make (synthesize) connective tissue. Smooth muscle cells contribute to a substantial bulk of the atherosclerosis lesion which may protrude several millimeters above the surface of the intima. As such, the artery becomes narrow, which reduces blood flow to tissues. A narrow coronary artery will reduce blood flow (oxygen & nutrients) to the myocardium: the heart muscle.

The proliferation of vascular smooth muscle cells has a significant role in the progression of atherosclerosis. Resveratrol has been found to inhibit the proliferation of vascular smooth muscle cells in culture.* Resveratrol is a polyphenolic compound found in the skin of red grapes.  Red wine is a rich source of resveratrol.

*Resveratrol Source:
Linus Pauling Institute
Oregon State University