Arterial wall thickening and loss of elasticity is termed as Arteriosclerosis, literally hardening of arteries.
There are 3 general patterns leading to this
Monckeberg medial sclerosis
We know that atherosclerosis affects mainly elastic and muscular arteries while HTN affects small muscular arteries and arterioles.
An overview of vascular architecture, thus becomes necessary.
All vessels except capillaries are organised into 3 concentric layers. Inner to outer being
Intima a single layer of endothelial cells over a thin basement membrane.
Media has several concentric layers of smooth muscle cells, elastic fibres
And the adventitia has loose connective tissue, nerve fibres and vasa vasorum.
Elastic arteries like the aorta have a high elastin content in media that helps them to recoil, while muscular arteries and arterioles predominantly have smooth muscle that help them better regulate regional blood flow and bp
Atherosclerosis is a lesion of the intima. This is composed of a fibrous cap and an atheromatous core and how this forms will be shortly reviewed.
So why is atherosclerosis so important?
Coronary artery disease, myocardial infarction, aortic and carotid atherosclerotic disease, stroke are some manifestations of atherosclerosis.
Other complications include thrombosis, embolism and aneurysm formation.
Now, before getting into the pathogenesis lets quickly review the major risk factors.
Modifiable risk factors include HTN, hyperlipidemia particularly hypercholestrolemia (very imp), cigarette smoking, diabetes, inflammation.
Constitutional or non modifiable risk factors include genetics, family history, age generally between 40 and 60 and male gender.
Hyperlipidemia is a major risk factor so lets review it a bit.
Plasma lipoproteins are spherical complex of lipids and proteins called apolipoproteins.
The lipoprotein includes chylomicrons, VLDL, LDL and HDL.
Now, chylomicrons have the highest percentage of triacylglycerols. They are transported from intestine to periphery.
The VLDL are produced in liver and carry endogenous triglycerides to periphery.
Then are the main villains, the LDL. About 70% plasma cholesterol is in LDL. Their main function is to provide cholesterol to peripheral tissues and also liver.
The highlight in our discussion is that the macrophages possess high levels of scavenger receptor activity that mediate endocytosis of chemically modified LDL in which the lipid or apo B is oxidised. Super highlight.
These receptors are not down regulated and ultimately there is accumulation of cholesteryl esters in macrophage forming foam cells.
Our heroes, the HDL serve to transfer cholesterol from periphery to liver for cholesterol homeostasis.
There is also a nearly identical structure to LDL called the lipoprotein (a) that is implicated in atherosclerosis. It has an additional apo(a) that is structually homologous to plasminogen, that is precursor of plasmin that dissolves blood clots.
So, basically high LDL-C and low HDL-C are risk factors for atherosclerosis.
With all this in mind lets look at the pathogenesis of atherosclerosis.
The model called the response to injury hypothesis highlights that atherosclerosis as a chronic inflammatory response, ultimately vascular healing driven by a variety of insults.
All this starts with chronic endothelial injury and dysfunction. Cigarette smoke toxins, high lipid levels, homocysteine, and disturbed or turbulent flow pattern seen at vessel branch points are all implicated in injury. Dysfunction results in increased permeability, leucocyte adhesion, monocyte adhesion and migration into intima forming macrophage and platelet adhesion and activation.
One of the most important cause of endothelial injury, chronic Hypercholestrolemia increases local ROS and decay of NO. In chronic hyperlipidemia, lipoprotein accumulate in intima, they get oxidised there by free radicals. This oxidised LDL is then taken up by macrophage and smooth muscle cells forming foam cells.
This leads to chronic inflammation as the macrophages have accumulated something abnormal.
Now starts the dangerous progressive cycle.
There is production of IL-1 that recruits leucocytes, monocytes and T lymphocytes.
This macrophage and T cell activation leads to production of cytopkines and chemokines that attract more and more inflammatory cells, producing more ROS, leading to enhanced lipid oxidation and more release of growth factors.
The PDGF leads to smooth muscle cell migration and proliferation.
Atheroma are dynamic lesion consisting of dysfunctional endothelial cells, smooth muscle cells, macrophages and T cells.
With progression, atheroma becomes modified with a prominent fibrous cap and a central core of lipid laden cells and fatty debris that can become calcified. The shoulders or the sides of the cap are more cellular and the periphery of the lesion demonstrates neovascularisation.
Now, to summarise
Atherosclerosis is an intimal lesion. In descending order, most extensively involved vessels are lower abdominal aorta, the coronary arteries, the popliteal arteries, the internal carotid arteries and the vessels of the circle of Willis.
The atherosclerotic plaque is susceptible to rupture or ulceration, hemorrhage, atheroembolism and aneurysm formation due to ischemic atrophy of the media.
With this we end this topic. Do subscribe to MedicaPods and stay tuned.