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Aragon also previously controlled the Duchy of Milan, but a year before Charles ascended to the throne, it was annexed by France after the Battle of Marignano in 1515.

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The Knight of Malta were part of the Holy League

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Barbarossa's naval victories secured Ottoman dominance over the Mediterranean during the mid 16th century, from the Battle of Preveza in 1538 until the Battle of Lepanto in 1571.

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Andrea Doria was the losing admiral at the Battle of Preveza

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Pope Paul III put forth the call for a Holy League against the Ottomans

The Republic of Venice urged Pope Paul III to assemble a Holy League against the Ottoman Empire

Hapsburg Empire during the reign of Charles V

Charles succeeded in re-capturing Milan in 1522 when Imperial troops defeated the Franco-Swiss army at Bicocca.

Francis I was taken at the Battle of Pavia in 1526