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For example, when this happens to the cardiovascular system, we call it
coronary artery disease
 (CAD),
angina
, or
congestive heart  ailure
 (CHF).Following this train o thought, I’ll start my discussion on health conditions with cardiovascular disorders.
The Role of Mitochondria in Cardiovascular Disease
Cardiovascular disease is a broad category o health conditions and is likely o great interest to the majority reading this book because it’s a leading cause o death globally (oen alternating with cancer or the top two spots, depending on the country you’re looking at). Conditions such as angina, hypertension, congestive heart ailure, ischemia, and diastolic dysunction all have their roots in mitochondrial energy. Not only can these conditions arise rom a cellular energy deciency, but they can also leak the purine building blocks o AP out o the cell. Interestingly, when purine building blocks leak rom the cell, they are metabolized to uric acid, and high uric acid in patients is oen refective o dysunctional AP metabolism (an important point to understand or clinicians treating gout, or example).It can take up to two weeks (and in some cases months) or the heart to produce enough AP, by natural, built-in mechanisms, to oset the decit caused by ischemia. Also, since the heart is constantly consuming AP, it’s dicult to make up or this energy decit quickly, and most patients with ischemia will need to take targeted nutritional therapy to help restore the energy balance. I’ll discuss these nutri-tional therapies in depth in chapter 3.
Understanding Smooth Muscles
A large part o our cardiovascular system involves smooth muscles (muscles not under voluntary control), so let’s review their signi-cance and what their normal and abnormal unctioning look like. Smooth muscles are ound in the blood vessels o the cardiovascular system, but are also contained within other organs and tubes in the body, including the stomach, intestines, bladder, airways, uterus, and
 
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the penile and clitoral cavernosal sinuses. Bundles o smooth muscle cells are also attached to the hairs o the skin and to the iris and lens o the eye. Smooth muscle cells receive input rom the autonomic nervous system (which is the part o the nervous system not under voluntary control, e.g., the part that digests ood). In addition to the autonomic nervous system, smooth muscles are controlled by hormones and other local chemical signals. Smooth muscle cells also develop tonic and phasic contractions in response to changes in load or length. By contrast, skeletal muscles are under voluntary control, and these are the muscles we consciously contract and relax when we decide to move our arms or go or a walk.Contraction (shortening o muscle cells) in smooth muscles is a highly regulated process. In some smooth muscle cells, the contrac-tion is maintained at a low level in the absence o external stimuli. Tis activity results in what is known as
smooth muscle tone
 and its intensity can be varied. Keep this in mind when I discuss how this relates to conditions such as hypertension (see “Coenzyme Q10” on page 144).Regardless o the stimulus, a smooth muscle contraction is initi-ated by calcium ions entering the cytosol (rom the sarcoplasmic reticulum—a membrane-bound structure in muscle cells that stores calcium) and binding to a calcium-binding messenger protein called
calmodulin
. Tis stimulates another protein called
myosin
 (the protein that contracts and is dependent on AP) to attach to actin in
cross-bridge cycling 
. Initiation o relaxation, on the other hand, begins with the removal o calcium ions rom the cytosol and stimulation o an enzyme that deactivates myosin (reerred to as
myosin phosphatase
).
The Importance of Smooth Muscle Relaxation
Many people don’t realize that muscle relaxation (elongation o a muscle cell) requires considerable amounts o energy. Whether it is a conscious decision to relax skeletal muscles or the involuntary relax-ation o smooth muscles, the process requires a decreased concentra-tion o calcium ions. All this calcium must move out o the cytosol
 
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and into the sarcoplasmic reticulum. However, this process requires the use o a pump because the calcium must move
up
 the concen-tration gradient—and going against the gradient requires energy. Tat energy, o course, comes rom AP. Te enzyme embedded in the membrane o the sarcoplasmic reticulum, called
calcium-magne-sium-ATPase
 (Ca-Mg-APase), when activated, binds two calcium ions, which are then transerred to the inner part o the sarcoplasmic reticulum and released (sequestered, ready or the next stimulus signaling a contraction). Tis pump also has two AP-binding sites, and both sites must have AP attached or it to work. However, there are intricacies. Te rst AP-binding site has a high anity or AP, and thereore, any AP in the vicinity binds to this site readily. Once bound to this site, AP releases its energy, and is turned into ADP. Te second AP-binding site does not attract AP so easily. In act, the only way or AP to bind to the second site is to ensure a high concentra-tion o AP so that hopeully one will just “all” into the binding site. Building up this concentration obviously requires signicant amounts o AP to be produced.Te state o rigor mortis, when our muscles become tense and rigid aer death, is a good example o how relaxation requires more AP than contraction. In death, uel and oxygen are no longer delivered to the muscles, and AP production stops. Without enough AP, the calcium ions cannot be pumped out o the cell, and the muscles can no longer “relax.”Magnesium ions are also necessary or the activity o the Ca-Mg-APase; they bind to the catalytic site o this enzyme to mediate the reaction. Without magnesium, this enzyme cannot unction and relaxation o the smooth muscle cannot occur (which can lead to things like high blood pressure, heart problems, or restricted breath-ing). For those who might have heard magnesium is great or muscle unction and relaxation but didn’t know how or why, now you know.
The Basics of Cardiac Physiology
Now let’s discuss the other part o the cardiovascular system: the heart itsel. Te human heart has our chambers—two upper chambers
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