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Small molecule and peptide therapy to lower LDL levels. A remarkable windfall in the discovery that α1PI regulates CD4 counts is that in doing so, α1PI incorporates the same mechanisms that regulate HDL and LDL levels. The same therapy that elevates CD4 counts in HIV disease also raised HDL (good cholesterol) and lowered LDL levels (bad cholesterol). There are several players involved, and this means the small molecules and peptides that are best for elevating CD4 counts may exhibit subtle differences from those that are best for lowering LDL levels. Best-in-class small molecules and peptides for both applications will be screened simultaneously.

Cardiovascular disease (CVD) is the leading cause of death and disability in the world and accounts for a third of deaths per year. The loss of one year of healthy life (disability-adjusted life years, DALY) due to CVD is assessed by the WHO as 160 million globally, and the estimated number of individuals with recognized or unrecognized CVD exceeds 2 billion. Globally, there were 17 million deaths due to CVD in 2008. The prevalence of CVD in the US is 81 million with 972,000 deaths due to CVD in 2008. There are currently 10 interventions and practices considered for cardiovascular disease :

1. Treatment of depression to improve mental health outcomes

2. Angiotensin-converting enzyme (ACE) inhibitor therapy

3. Angiotensin II receptor blocker (ARB) therapy

4. Anticoagulant Therapy

5. Antiplatelet therapy

6. Antiplatelet therapy post stent placement

7. Beta-blocker therapy

8. Calcium channel blocker therapy

9. Lifestyle modification

10. Treating comorbid conditions (hypertension, lipid management)

Targeting HDL and LDL transport via α1PI regulation is an additional 11th intervention that does not overlap the 10 current recommended interventions and practices. Of considerable importance, targeting HDL and LDL transport via α1PI regulation directly targets the natural pathway for regulating LDL levels.

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