Atherosclerosis Quiz

Lecture 11: Atheroma

• Atheroma is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium-sized arteries.
• Atheroma forms as a raised focal lesion within the intima, with a soft, yellow core of lipid (primarily cholesterol esters). A firm, white fibrous tissue layer surrounds this core, potentially obstructing blood flow and weakening underlying artery walls.
• Arteriosclerosis is a broader term for thickening and loss of arterial wall elasticity. Three main types exist: atherosclerosis, Mönckeberg medial calcific sclerosis (calcification in muscular arteries in those over 50), and arteriolosclerosis (affects small arteries and arterioles).

Intended Learning Outcomes

• 1 ) Defining and describing Atheroma, Atherosclerosis, and Arteriosclerosis including their cellular events and morphological appearances (macroscopic and microscopic).

• 2) Effects of severe atherosclerosis at specific anatomical locations needing to be understood.

• 3) Explaining the mechanisms of atherogenesis, focusing on the roles of growth factors (e.g., platelet-derived growth factor (PDGF)), the response to injury hypothesis, and dyslipidaemias.

• 4) Epidemiology of Coronary Heart Disease, including the description of coronary risk factors in atherogenesis, along with genetic, geographic, and ethnic susceptibility to this disease.

Cell Types Involved in Atheroma Formation

• Endothelial cells
• Smooth muscle cells
• Macrophages
• Platelets
• Neutrophils
• Lymphocytes

Cellular Events Leading to Atherosclerotic Lesions (Endothelial Cells)

• Endothelial cells play a critical role in haemostasis, maintaining blood-tissue interface, modulating blood flow and resistance.
• Endothelial cells may have altered permeability to lipoproteins.
• They secrete collagen.
• They stimulate smooth muscle cell proliferation and migration.
• Loss of endothelial cells (denudation) triggers thrombosis and smooth muscle cell proliferation.

Cellular Events Leading to Atherosclerotic Lesions (Vascular Smooth Muscle Cells)

• Vascular smooth muscle cells migrate to the intima and proliferate after injury. They are crucial for both normal repair and pathological processes like atherosclerosis.
• Smooth muscle cells can take up LDL and other lipids, converting into foam cells.
• Synthesis of collagens and proteoglycans occurs.
• Injury to the endothelium (acute or chronic) promotes smooth muscle cell growth. Repair mechanisms involves neointima formation with smooth muscle cells migrating from the media to the intima, proliferating, and producing ECM.

Cellular Events Leading to Atherosclerotic Lesions (other cell types)

• Lymphocytes: affecting lipoprotein metabolism and stimulating smooth muscle cell proliferation and migration.
• Platelets: playing a key role in haemostasis, and stimulating smooth muscle cell proliferation and migration (PDGF).
• Macrophages: oxidizing LDL, engulfing lipid to become foam cells, releasing proteases, and stimulating smooth muscle cell proliferation and migration.

Processes Involved in Atheroma Formation

• Thrombosis
• Lipid accumulation
• Production of intercellular matrix
• Interaction between cell types

Types of Atheroma Lesions

• Several types of atheroma lesions exist based on their stage. Details of their histology and progression phases are listed.

Morphological Appearance of Atheroma

• Fatty streaks: the earliest lesion of atherosclerosis characterized by lipid-filled foam cells, seen as flat yellow spots.
• Simple plaques: Raised yellow/white lesions with irregular outlines. They are widespread and can merge together.
• Complicated plaques: have characteristics of thrombosis, haemorrhage, inflammation, and possible aneurysms.

Risk Factors for Atheroma

• Age: progressively increases from youth to adulthood, and risk factors persist over time. While women are often protected before menopause, hormonal changes and other factors play a role in individual risk.
• Hyperlipidaemia: High plasma cholesterol, specifically LDL cholesterol, is a significant risk factor.
• Smoking: a significant risk factor.
• Hypertension: a strong link with IHD, and is thought to damage endothelium.
• Diabetes mellitus: significantly increases IHD risk, and links to increased risk of cerebrovascular and peripheral vascular disease.
• Alcohol intake: moderate or high alcohol intake increases the risk of IHD. (over 5 units per day).
• Infection: including Chlamydia, helicobacter pylory have recently been associated with a risk, though this correlation is still being investigated.
• Other genetic or acquired disorders: (e.g., diabetes mellitus, hypothyroidism) can lead to hypercholesterolemia, increasing premature atherosclerosis risk.
• Inherited blood lipid disorders: inherited defects in lipid metabolism or lipoprotein uptake also increase the risk of hyperlipidemia.

Response-to-Injury Hypothesis

• The model views atherosclerosis as a chronic inflammatory and healing response of the artery wall to endothelial injury.
• Lesion progression arises from the interaction of modified lipoproteins, monocyte-derived macrophages, and T lymphocytes with normal arterial constituents.
• Endothelial injury is a key driver, increasing vascular permeability, enabling leukocyte adhesion, and facilitating lipoprotein accumulation (primarily LDL, and its oxidized forms).
• Platelet adhesion, resulting from factor release, induces smooth muscle cells recruitment (from media or circulating precursors).
• Lipid accumulation occurs both extracellularly and intracellularly in macrophages and smooth muscle cells.

Coronary Heart Disease and its Effects

• Ischemic heart disease
• Sudden death
• Myocardial infarction
• Angina pectoris
• Arrhythmias
• Cardiac failure
• Cerebral ischaemia
• Transient ischemic attack
• Cerebral infarction
• Multi-infarct dementia (etc.)
• Mesenteric ischaemia
• Ischemic colitis, malabsorp
• Intestinal infarction, aortic aneurysms
• Peripheral vascular disease.
• Intermittent claudication.
• Leriche syndrome
• Ischemic rest pain
• Gangrene

Prevention of Atheroma

• Stop smoking
• Modify diet
• Treat hypertension
• Treat diabetes
• Lipid-lowering drugs
• Address genetic predisposition, geographic risk

Other Important Points about Atheroma

• Endothelial dysfunction: a primary etiologic factor in atherosclerosis involving increased permeability, leukocyte adhesion and thrombus formation, caused by hypertension, hyperlipidemia, cigarette smoking, homocysteine, and even some infectious agents.
• The importance of lipids: These are not just in the blood, but also in the arterial wall itself, which changes over time. LDL is commonly associated with problems like atherosclerosis, while HDL helps remove cholesterol.