The thrombus is also in danger of breaking from the site and traveling through the arteries. The blockage caused by a thrombus can be life threatening. A blockage in the coronary arteries may cause a heart attack while blockage in a cerebral artery may cause a stroke. The number of vasa vasorum was quantitated manually with the aid of computerized morphometry on sections stained immunohistochemically for endothelial cells with antibodies against factor VIII—related antigen.
Postmortem evaluation of levels of total cholesterol TC , high-density lipoprotein cholesterol HDL-C , glycosylated hemoglobin, and thiocyanate as a marker for cigarette smoking and evaluation for hypertension was performed as previously described. In exertion-related deaths, information from the scene and next of kin was obtained to estimate if the individual performed exercise routinely as part of a regimen several times per week or was sedentary.
Cases were excluded if there was gross hemolysis or if evaluation of total protein and serum albumin levels indicated hemoconcentration or hemodilution. The body mass index was estimated as weight in kilograms divided by the square of height in meters.
Investigators at the scene of death recorded the circumstances of death, including the decedent's activity, in each case. In deaths that were not witnessed, the location of the body and clothing were recorded, and an assessment to the probable activity prior to the terminal event was made in each case.
The exertional status was defined as rest patient found in bed, in a reclining position, or apparently ambulating in the performance of day-to-day activities , physical exertion, or emotional stress. Physical exertion was defined as the performance of a sport during or within 1 hour of the cardiac arrest, heavy lifting, strenuous digging or shoveling, or sexual activity. Emotional stress was defined as a witnessed verbal altercation with physical involvement eg, chasing, hitting, or posturing occurring within 2 hours of the cardiac event, public speaking, or involvement in another fear-inducing activity eg, fire fighting.
For univariate analysis, unpaired t tests were used to compare continuous variables of risk factors and other parameters in the exertion group vs the rest group.
When these parameters were analyzed for the different groups of exertion, an analysis of variance ANOVA means table with Fisher ad hoc test was used. Multiple logistic regression was performed with risk factors independent variables, including exertional status and presence of plaque rupture dependent variable for multivariate analysis. For multivariate analysis examining the association of risk factors with numbers of vulnerable plaques, for both exertion and traditional risk factors, ANOVA was performed.
A total of hearts were studied. One hundred thirteen cases, comprising the earliest two thirds of the current cases, have been published previously but without data regarding activity at death or medication use. There were whites, 34 blacks, and 1 Asian. The deaths were witnessed in 90 cases and not witnessed in 51 cases. Fourteen of the 25 deaths related to exertion occurred in previously sedentary men who were engaged in sudden strenuous activity: carrying heavy objects unloading a truck [2], moving heavy furniture [2], pushing a car [1] ; lawn mowing 2 ; having sexual intercourse 2 ; ditch digging 1 ; playing basketball 2 ; bicycling 1 ; and shoveling snow 1.
In 4 men, death occurred during physical activity that had been performed on a regular basis: swimming 1 , exercising on a stationary cross-country ski machine 1 , and running 2. Seven of the 25 exertion deaths occurred during emotional exertion: verbal presentations before an audience 2 , verbal and physical altercation 3 , court appearance 1 , and fire fighting 1.
Of the nonexertional deaths, 62 occurred at home, 13 while driving, 4 in hotel rooms, 26 at work, and 11 outdoors. Of the 62 men who died at home, 20 died apparently while sleeping, 5 died while in the bedroom watching television, 3 died in the kitchen, 26 died in the living room or family room, and 8 died in a workshop or the basement. The 13 automobile drivers who died suddenly were involved in automobile crashes. However, there were no cases of significant trauma at the time of the cardiac arrest, and all but 1 police report excluded any possibility of near collision with another automobile or possible "road rage" or other inciting event.
In most of these cases, witnesses or passengers indicated that the driver had an apparent "heart attack. The 4 men who died in hotel rooms were found alone and apparently had been involved in sedentary activities. The 26 men who died while at work were involved in nonstrenuous activities or activities that were repetitive in nature and did not involve lifting heavy objects. The 11 men who died while outdoors were performing various activities not related to exercise, heavy labor, or lifting but were walking in the yard or toward a car or a bus, eating, leaving a meeting place or entertainment area, or walking by the roadside.
The characteristics of the study subjects are shown in Table 1. There were no significant differences between men whose deaths occurred during exertion vs those at rest in age, body mass index, or levels of TC or HDL-C. There were no significant differences in other risk factors between men with sudden death occurring during exertion vs rest.
The mean SD glycosylated hemoglobin reading was 7. The culprit plaque in the 25 hearts in the exertion group was acute plaque rupture in 17, healing plaque rupture in 0, stable plaque in 6, and plaque erosion in 2. In the hearts in the rest group, the culprit plaque was acute plaque rupture in 27, healing plaque rupture in 5, stable plaque in 60, and plaque erosion in The proportion of abnormal cholesterol values was highest in the plaque rupture exertion group, followed by men dying at rest with plaque rupture, at exertion with stable plaque or healing plaque ruptures, and at rest with stable plaque Table 2.
The mean SD number of vulnerable plaques in the coronary arteries of each heart in the exertion group was 1. In the 44 hearts with acute plaque rupture, the site of rupture shoulder region, mid cap, circumferential could be determined in 36 cases, and in 8 cases the destruction was too great to determine the exact site of plaque rupture. The 36 cases included 20 men who died while at rest and 16 men who died during exertion.
Of these 20 rest cases, the site of plaque rupture was the shoulder region in 13 Figure 1 , mid cap in 6, and circumferential in 1. This can cause a heart attack or stroke. This theory suggests that atherosclerosis develops as a result of repetitive injury to the inner lining of the artery.
Injury may stimulate cells to grow and divide as part of the inflammatory process. This normal, healing response to chronic injury may actually result in the growth of atherosclerotic plaque. Smoking plays a large role in the development of atherosclerosis. The carbon monoxide and nicotine contained in tobacco smoke affect blood flow through your arteries by:.
Atherosclerosis is one of the major causes of abdominal aortic aneurysm. The wall of the aorta and all blood vessels is a dynamic tissue made up of living cells that need nutrients and oxygen. Many of these nutrients seep from the inside of the blood vessel through the walls to nourish the rest of the blood vessel. When the inner lining of the vessel is covered with an atherosclerotic plaque, nutrients can no longer seep through sufficiently.
The cells receive no oxygen, and some of them die. As the atherosclerosis progresses and cells continue to die, the walls become weaker and weaker. At some point, a critical relationship is reached between the pressure experienced in the center of the blood vessel, the wall tension, and the strength of the wall itself.
When this point is reached, the wall begins to dilate grow larger in the area of the plaque. As the diameter of the vessel grows, the wall tension increases, leading to even more dilation. The end result is an aneurysm. Author: Healthwise Staff. Medical Review: Rakesh K. This information does not replace the advice of a doctor. Healthwise, Incorporated, disclaims any warranty or liability for your use of this information.
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Updated visitor guidelines. Three major families of enzymes participate in extracellular matrix degradation: serine proteases urokinase and plasmin , cysteine proteases such as cathepsins, which are largely intracellular enzymes, and matrix metalloproteinases MMPs.
Degradation of extracellular matrix requires a two-step process: 1 enzymatic disruption of the extracellular milieu; and 2 clearance via endocytosis of the degraded components and lysosomal degradation. MMPs are an important family of enzymes in the initial stages of degradation and have been the focus of increasing research [37]. The proenzyme includes an N-terminal domain which is cleaved when the enzyme is activated, in addition to catalytic and C-terminal domains.
The latter two domains are involved in receptor identification and specificity of substrate recognition as well as being the site where the endogenous inhibitor called tissue inhibitor of metalloproteinases binds on a stoichiometric basis. MMP activity is substrate-specific, although substantial substrate overlap exists among the various members of this family of enzymes. Activation of MMPs can occur through several mechanisms that usually involve cleavage of approximately 10 kilodalton from the N-terminus of the proenzyme.
In the atheroma, activation can be mediated by reactive oxygen species [38] or plasmin. Lijnen et al. At least three types of MT-MMPs are expressed in vascular smooth muscle, and these proteins may participate in regulation of matrix weakening [40]. Overexpression of MMPs has been demonstrated in atheromatous lesions both in animals and humans. Nikkari et al. A potential sequence of events leading to elevated levels of MMPs in the plaque begins with ingestion of lipids by infiltrating macrophages into the atheromatous lesion.
Galis et al. Another component of atheroma architecture in plaque stability is the lipid core. Its mechanical properties affect the distribution of tensile forces, making stresses concentrate in the fibrous cap, particularly at its edges. Clinical trials using lipid-lowering agents have shown an improvement in morbidity and mortality from cardiovascular diseases [43].
A potential mechanism explaining this effect might be changes in the composition of the lipid core by decreasing cholesterol esters and increasing the proportion of insoluble cholesterol monohydrate. These changes would potentially decrease the degree of stress affecting the fibrous cap [44].
Several investigators have noted an association between overexpression of MMP-1 and the shoulder regions of the atheroma, which are also the regions of increased mechanical stress. We studied the localization of MMP-1 quantitatively by comparing the distribution of stress in human coronary lesions with the expression of MMP Expression of MMP-1 increases severalfold in regions of increased mechanical stress [45].
Since this is where plaque rupture frequently occurs, it is attractive to speculate that the combination of excess matrix degradation and excess mechanical stress at these locations leads to failure of the fibrous cap. This raises the intriguing question that the increased stress in these regions actually promotes weaker extracellular matrix. One possible source of MMPs in the fibrous cap shoulders is the VSMCs, although the unstable fibrous cap has a reduced number of these cells.
Mechanical signals are powerful regulators of cellular functions, and it has been known for over 20 years that mechanical deformation regulates extracellular matrix synthesis by VSMCs [46] , and reviewed in Ref. Multiple transduction pathways may participate in converting mechanical signals into biochemical signals, including stretch-activated ion channels, paracrine growth factors, G proteins, MAP kinases, integrins, tyrosine kinases, and phospholipid metabolism.
No single gene or signaling pathway seems to be responsible for all mechanotransduction; in different experimental conditions, different pathways may predominate [48—50].
Thus, direct induction of MMP-1 by increased mechanical stress on VSMC in the high stress region of the atheroma is not supported by in vitro data [51]. An alternative possibility is that MMP-1 is increased directly or through paracrine mechanisms involving the macrophage. Currently, little is known about how macrophages respond to mechanical stimuli. Martin et al. They identified an outwardly rectifying potassium channel that is inactive at rest but activated by adhesion of cells or stretch of the membrane.
This demonstrates that macrophages, like smooth muscle cells [53] , have stretch-activated channels which can transduce mechanical signals.
Mastsumoto et al. They found evidence suggesting that cyclic stretch inhibits the differentiation to vacuolized cells and facilitates the differentiation to spindle cells [54]. Thus, it is possible that macrophages are particularly active in this region of increased mechanical stress.
By understanding factors that regulate extracellular matrix integrity in the atheroma, we may potentially pharmacologically modify lesion stability in the future.
One theoretical disadvantage of this approach is that by downregulating matrix degradation, total volume of the atheroma could increase. This would lead to an increase in chronic ischemia; one could argue that chronic ischemia is more easily managed than an acute vascular catastrophe.
However, recent animal evidence suggests that both reduction in lesion mass and improved stability may be possible. When Aikawa et al. In the past decade, a wealth of insight into the nature of the unstable atheroma has emerged. The success of cholesterol-lowering therapy indicates that plaque rupture is not the inevitable natural history of the atheroma. We now recognize that plaque stability is determined by many factors, including extracellular matrix degradation, mechanical forces caused by lipid deposits, and inflammation.
Currently we do not know the cadence of instability, although recent epidemiological studies suggest that inflammation precedes clinical events by many years [56]. This potentially provides us with a prolonged window of opportunity to intervene before lesions cause acute events. As the global importance of acute ischemia is increasing, we must learn more about how to identify unstable lesions and reverse the processes that lead to plaque rupture. Because plaque rupture is a catastrophic mechanical event, understanding the interactions between mechanical forces and extracellular matrix integrity will be essential.
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