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Keep Out The Rain

cvd umbrella

It has been well established that cardiovascular disease (CVD) is a condition that leads to chronic symptoms that are generally thought of as a primary disease. However, vascular injury leads to subsequent disease such as metabolic disease, obesity, high blood pressure and kidney disease. There are several contributing factors starting a person on the path of having cardiovascular disease. Some of these include:

  1. Oxidative (ox)stress—potentially results in DNA damage
  2. Increased low density lipid (LDL) that can become oxidized into oxLDLs
  3. Overeating/over-nutrition leads to hormonal imbalances and subsequently obesity and/or metabolic disease
  4. Distress/Eustress is controversial, but the body does not know the difference and they can both lead to shear stress due to increased blood flow through laminar areas of the vascular system.
  5. Toxins that come produced within the body (endobiotics) or enter the body from outside source (xenobiotics). Environmental effects have strong impacts on how the body responds. It is important to manage the things that are within one’s control such as smoking, exercise, and consuming a well-balanced diet.

With people livings becoming busier, it is easy to miss the warning signs. A slight weight gain here or a headache there. What then can be done about the progression of CVD and other disease states such as hypertension? I am glad you asked. Controlling hypertension for example can be maintained by making lifestyle changes consisting of exercising at least 150 minutes per week, modifying one’s diet to potentially include the dash diet, and reducing stress levels. This sounds like a lot but planning ahead is key. Often times I find myself going to a fast food restaurant because I have gotten too hungry to cook, or because I have not had time to go shopping. When I plan ahead and purchase my food for a week and pack healthy snacks, I evade the urge to go for those french fries (my go-to weapon against hunger). Additionally, I find I am less stressed if I spend some time performing rigorous exercises or get moving throughout the day. I attempt at least 250 steps every hour and 10,000 steps over the course of the day.

However, the symptoms are not the same for everyone, thus one should know what to look for to identify vascular disease early as well as forming a trusting relationship with a primary care provider because, “You’re the Cure”!! Let’s keep this conversation going. Follow me on Twitter (@AnberithaT) or on my site. I will take a deeper look at each of these topics and discuss what, if anything, can be done to combat or control these symptoms.

 

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Apoptosis, Necrosis, and Necroptosis – Are They Important in Vascular Injury?

Have you ever wondered the difference between necrosis and apoptosis and how that relationship relates to vascular injury? What about whether they can be one and the same at any point in the cell death process?

Cellular death can be either natural or trauma induced.  The primary difference between the two is that the necrotic pathway consist of the premature death of cells and tissue from a cause of factors, such as infection, toxins, or trauma. Necrosis can often time lead to the detriment of the organ system and/or organism.  Whereas, apoptosis provides beneficial effects to the organism –  a process of programmed cell death that is a result of housekeeping pathways.  It produces cell fragments called apoptotic bodies that engulf and remove contents of a damaged cell before it can become toxic to an organism.  For example, in the vessels, macrophages engulf oxidized low density lipoproteins (oxLDLs) resulting in foam cells. These oxLDL are not metabolized properly causing the cell to undergo apoptosis. The result is chronic inflammation.

With that being said, the apoptotic pathway acts in the Fas receptor (Apo-1 or CD95) in the binding site of the transmembrane protein part of the fas ligand (FasL).  Interaction between Fas and FasL results in the formation of a death-induced signaling complex.  A primary mechanistic cause of cell death is the proteolytic caspases; enzymes that initiating the degradation of the cellular organelles leading to cell shrinkage and rounding due to the proteinaceous cytoskeleton by caspases.  The caspases that are suggested to initiate this programing are FADD, caspase-8 and caspase-10. However, there are other pathways that can induce apoptosis, which are not lucid.  Since FasL plays an important role in the immune system and the progression of cardiovascular disease and cancer, it will bind to TNF to induce apoptosis of the immune cells in attempt to increase the number of healthy cells and, in the case of atherosclerosis, eliminate the lipid laden cells in the vessel wall.

Necroptosis is a relatively novel form of necrosis. This pathway suggests necrosis can be programmed, favoring the immunogenic nature of defense against a pathogen by the immune system. Being a caspase independent pathway, necroptosis allows cells to undergo the suicide process in the presence of viral caspase inhibitors to contain the virus to a specific region. Necroptosis has been shown to play a role in disease processes such as autoimmune diseases, pancreatitis, and myocardial infarction using TNFα and its receptor TNFR1 that is associated with TRAF2 signaling. Phosphorylation of MLKL allows for the insertion of permeabilized plasma membranes leading the release of damage-associated molecular patterns initiating the inflammatory response. The growing relevance of necroptosis is the pathophysiology can lead to the understanding of many pathologies such as acute tissue damage including hypertension, myocardial infarction, stroke, ischemia-reperfusion injury, and atherosclerosis as well as some cancers. Ischemia-reperfusion injury is a major burden of organ transplants, thus contributing to tissue damage resulting from activation of the necroptosis pathway. Understanding this pathway, could be a seductive means of controlling vascular injury.

What are your thoughts on this topic? I am interested in learning more about this as a viable research focus for the cardiovascular therapeutic area.