Cerebral Atherosclerosis: Causes

Pathogenesis (disease development)

Small lesions (injury) that may be present in the arterial wall as early as adolescence constitute the asymptomatic beginning of atherosclerosis. In the first place, endothelial cell damage (so-called endothelial dysfunction; endothelium = cells of the innermost wall layer directed toward the vessel lumen) is caused by an increased supply of oxidized LDL, (low-density lipoprotein; German: Lipoprotein niederer Dichte) especially by small, dense LDL particles (“small dense LDL”). The further steps of atherogenesis (development of arterial calcification) are:

  • Attachment of monocytes (belong to the white blood cells; precursors of macrophages, which play an important role in immune defense as “scavenger cells”) and platelets (blood platelets; blood cells that are important for blood clotting) to the dysfunctional endothelium.
  • Immigration of monocytes and platelets into the intima (innermost layer of the vessel wall)
  • Monocytes become macrophages and ingest LDL particles
  • Macrophages give rise to foam cells (foam-cells), which become lodged in intima and media (middle layer of arteries, depending on the type of vessel, consisting of a more or less distinct muscle layer) and lead to inflammatory reactions (→ fatty streaks; fatty streaks)
  • Endothelial cells and monocytes produce increased cytokines and growth factors (→ proliferation of smooth muscle cells of the media)
  • Migration of smooth muscle cells into the intima and synthesis of collagen and proteoglycans (extracellular matrix; extracellular matrix, intercellular substance, ECM, ECM) leads to the formation of fibrous plaques.
  • Demise of foam cells in the fibrous plaques (→ release of lipids and cholesterol); Ca2+ incorporation results in cholesterol crystals.
  • The media is completely affected by the above process in the final stage and thus loses its elasticity

Unstable plaques are particularly dangerous, the rupture of which can lead to acute vascular occlusion (e.g., myocardial infarction/heart attack). Particularly dangerous are unstable plaques whose rupture can lead to acute vascular occlusion (e.g., myocardial infarction/heart attack). In pathogenesis, the adventitia (tissue surrounding the vessel on the outside) is currently the focus of research. This is useful because it is the only way to understand the differential involvement of individual stromal areas. Another research focus in atherosclerosis research is the investigation of microbiological causes of atherosclerosis. Questions seeking answers are: What causes infection with the vasa vasorum (smallest arteries and veins found in the wall of larger blood vessels) and why are they damaged? Why do localized infections affect vessels far from the focus, such as the aorta (main artery)? How can environmental toxins, infections and other factors trigger the same mechanism of damage? Haverich, director of the Clinic for Cardiothoracic, Transplantation and Vascular Surgery, in Hannover at the MHH, challenges the previous doctrine and argues that the fatty deposits. the so-called plaques, do not come from the blood, but are remnants of dead cells of the vessel wall. He sees this as caused by inflammatory reactions caused by viruses, bacteria and particulate matter, which lead to the occlusion of the vasa vasorum and thus to the death of the tunica media (media; middle wall layer of a vessel/muscle layer). Thus, atherosclerosis of the adventitia (tissue surrounding the vessel to the outside) would run through the outer wall of the arteries into the media and intima. It would thus be a microvascular disease of the adventitia.and plaques would be the result of immune system repair processes.

Etiology (Causes)

Biographic Causes

  • Family history – coronary artery disease (CAD) or myocardial infarction in close relatives (1st degree) – especially if men develop the disease before the age of 55 years or women before the age of 65 years, respectively; presence of atherosclerosis-related vascular disease
  • Age – increasing age

Behavioral causes

  • Nutrition
    • Malnutrition and overeating, e.g., excessive caloric intake and high-fat diet (high intake of saturated fat).
    • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
  • Consumption of stimulants
    • Alcohol (woman: > 40 g/day; man: > 60 g/day) – (hypertriglyceridemia).
    • Tobacco (smoking) – smoking is one of the central risk factors for atherosclerosis and thus for all cardiovascular diseases
  • Physical activity
    • Physical inactivity
  • Psycho-social situation
    • Psychological stress
    • Stress
    • Sleep duration ≤ 6 hours vs. 7-8 hours of sleep (+27% increased risk of vascular plaque formation)
  • Overweight (BMI ≥ 25; obesity).
  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – there is a high waist circumference or waist-to-hip ratio (waist-to-hip ratio); increased abdominal fat has a strong atherogenic effect and promotes inflammatory processes (“inflammatory processes”)When measuring waist circumference according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
    • Men < 94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

Disease-related causes

  • Arterial hypertension (high blood pressure)
  • Depression
  • Diabetes mellitus (insulin resistance)
  • Hyperlipidemia/dyslipidemia (lipid metabolism disorder) – hypercholesterolemia; hypertriglyceridemia.
  • Hypothyroidism (hypothyroidism) – this is usually accompanied by elevated serum cholesterol levels; latent (subclinical) hypothyroidism is also a risk factor for atherosclerosis
  • Metabolic syndrome
  • Osteoporosis – significant risk factor for coronary heart disease (CHD): this is explained by the fact that the so-called osteoclasts (bone-degrading cells) – also stimulate sclerosis (calcification) of the arteries.
  • Periodontitis (inflammation of the periodontium).
  • Subclinical inflammation (English “silent inflammation”) – permanent systemic inflammation (inflammation affecting the entire organism), which proceeds without clinical symptoms.

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Apolipoprotein E – genotype 4 (ApoE4).
  • CRP (C-reactive protein)
  • Cholesterol – total cholesterol, LDL cholesterol, HDL cholesterol.
  • Fibrinogen
  • Hyperhomocysteinemia
  • Lipoprotein (a)
  • Fasting insulin
  • Triglycerides

Environmental pollution – intoxications (poisonings).

  • Air pollutants: particulate matter

Other causes

  • Infections:
    • Chlamydia pneumonia
    • Cytomegalovirus (CMV)
    • Porphyromonas gingivalis (periodontitis germ).
  • Chronic infections – for example, urogenital tract, respiratory tract.